A brilliant student and one of the five original X-Men, McCoy completed his doctoral studies under Xavier’s tutelage, and finally left the X-Men and Xavier’s school to take a position as a genetic researcher with the Brand Corporation. There he developed a serum that acted as a catalyst for activating latent mutations. Upon drinking the serum McCoy underwent radical physical changes. He grew fur over his entire body, his ears became larger and pointed, and his canine teeth became larger, resembling fangs. The serum also increased his superhuman agility, endurance, speed, and strength.

Eventually, McCoy left Brand, joined the Avengers, and publicly revealed his dual identity. After years of service with the Avengers (during which he also aided the X-Men against Dark Phoenix), the Beast took it upon himself to reorganize another super-hero group, the Defenders, into a more formal combat organization. His X-Men cohorts Angel and Iceman served in the Defenders along with him, but the team collapsed after a climactic battle in which several other members seemingly perished.

Subsequently, the Beast and his fellow members of the original X-Men formed a new organization, the original X-Factor, which publicly appeared to hunt down allegedly dangerous mutants but secretly taught them how to use their superhuman abilities. Shortly after the formation of X-Factor, the Beast was captured by the geneticist Dr. Carl Maddicks, who performed an experiment that caused the Beast to revert to his original, more human appearance. Some time later, however, the mutagenic powers of the mutant Infectia triggered the Beast’s return to his furry, more animalistic appearance. After Professor Charles Xavier returned to Earth following an extended stay in outer space with the Starjammers, the Beast and his fellow X-Factor founders returned to the X-Men.

Beast served as the resident technological and medical genius at Professor Xavier's, working on everything from advanced alien technology to the mutant-killing Legacy Virus while also serving as an active member of the X-Men's Blue Team. He even became field leader at one time. At this time, Hank began calling Scott "Fearless Leader". After Prof. Xavier was shot by Stryfe, Beast and Dr. Moira MacTaggert worked diligently to cure him of the Techno-Organic Virus ravaging his body, until Apocalypse stepped-in and provided the cure. Hank found the challenge of his career once Stryfe tricked Mr. Sinister into releasing the deadly Legacy Virus. During a televised debate Hank smeared political candidate and mutant hater, Graydon Creed.

In San Francisco Hank and Bobby visited Infectia who was dying from the Legacy Virus. There, they met a young mutant, Threnody, who could sense the Legacy Virus's effects. Hank decided to leave her in Sinister's care, hoping that because of his lack of morals, Sinister could find a cure to the Legacy Virus with her help. Hank held the dying Infectia in his arms as she watched her final sunrise. After months with no progress on the Legacy Virus, Hank used information provided by Sabretooth to lead a small team of X-Men to Scott's old orphanage, The State Home for Foundlings in Omaha, Nebraska. The team found Threnody in a workshop, working to cure the Legacy Virus for Sinister. This time, Hank had a change of heart and refused to let her stay in Sinister's care. Threnody promised the X-Men that she would work for them while gaining Sinister's trust, warning they should leave before Sinister became aware of their presence. Hank disagreed, but was forced to accept her decision. Trish broke the news that the Legacy Virus, initially a mutant virus, was now affecting humans, putting more strain on her relationship with Hank. Hank participated in a press conference with Professor Xavier to calm the populace over the threat of the Legacy Virus in San Francisco.

Hank's counterpart from an alternate reality, the Dark Beast, was startled to see his counterpart working with the X-Men. After Dark Beast researched Hank, from visiting (and killing) his elementary school principal, his old girlfriend Mindy, his priest, his parents (who he couldn't bring himself to kill, but killed an innocent bystander instead), and apparently members of his high school, Hank was kidnapped by his alternate self in an attempt to hide from this reality's Sinister. Hank was kept alive at the abandoned Brand Corporation building, just in case the Dark Beast would need more information while impersonating him. Hank was trapped while Dark Beast took over his life as an X-Man and his research, including the work on the Legacy Virus. Hank escaped at the same time that Dark Beast was discovered by Onslaught. Upon returning to the team, Hank met Trish and the two reconciled their relationship.

Dr. MacTaggert, the only human to contract the virus, discovered a cure to a certain strain after Mystique's irresponsible manipulation to the virus. She died delivering the data to Professor Xavier's, leaving her work incomplete. Based on Moira's notes and his work combined, Beast finished the anti-virus, but discovered that in order for it to work he needed a sample of an infected mutant. Acting before anyone could stop him, Colossus decided to sacrifice his life. Hank spent a short time with Storm's X-Treme team, in search of Destiny's diaries. Hank underwent a Secondary Mutation, that caused him to mutate further into a more feline creature, after having his "latent genetic potential" jump-started by Sage. After Vargas killed Psylocke, Beast returned to the Institute. The combination of the loss of a friend and his further mutation caused Beast to become very insecure, feeling that he was devolving into an animal. Hank withdrew deep into his work, helping Prof. Xavier build a stronger Cerebro, named Cerebra. Prof. Xavier opened the school to a larger student base and publicly announced that he was a mutant. Hank finally ended his relationship with Trish, as she was afraid what would happen to her image if she was seen with him in public. After he discovered the mad Cassandra Nova was inhabiting Prof. Xavier's body, Nova manipulated his student Beak into beating Beast into a deep coma. Nova left him with the thought that his secondary mutation was actually de-evolution and that he would soon have the intelligence of a house cat. Hank eventually woke up just in time for Jean and Emma to perform a psychic surgery and keep Prof. Xavier alive.

Over time, Beast struck up a strong friendship with Emma, even collecting her shattered diamond form and arranging thousands of pieces into place, after she was attacked by Esme Cuckoo. Hank began falsely claiming he was gay to the public, in the hope of inspiring wider support for tolerance. Hank finally found his place as a guidance counselor. Hank began to question his intentions as far as mutant rights went, firstly during Dr. Kavita Rao's so-called cure for mutation, then after the events of House of M. Emma found that he was considering taking the serum, but after a fight with Wolverine in front of the students, and Cyclops asking him to wait on it, Hank decided otherwise. Beast began dating S.W.O.R.D. agent, Abigail Brand. During the Civil War, Beast, was among the original X-Men that helped Bishop rescue the trapped 198 and also provided Spider-Man with a holographic disguise, then enlisted in the Initiative program.

Hank endeavored to find a way to reverse the de-powering effects of M-Day, and thus prevent the extinction of the mutant race, as not only had most of the current mutants lost their powers, but no new mutants were developing powers. To this end, Beast enlisted numerous villains, after having exhausted the help of the likes of Reed Richards and Tony Stark, to help him understand the situation. The scientists he contact were Doctor Doom, Mr. Sinister, the High Evolutionary, Dr. Kavita Rao, Mojo, Sugar Man, Arnim Zola, M.O.D.O.K., Spiral and Pandemic. He gives them a detailed history of M-Day and the events that followed, including the work he and various other brilliant scientists have tried in finding a cure. The Beast then asks them for their help, offering in return the myriad of discoveries that he has made. Hank traveled to Transia in search of the High Evolutionary, whose earlier cryptic comments aroused Hank's curiosity. Scaling Mount Wundagore, Hank and his group of travelers were confronted by the Knights of Wundagore. Hank began working with Dark Beast, until at the Guthrie home, the Dark Beast injected one of the non-mutant children with a serum as a test subject. Hank eventually decided to track down the Scarlet Witch, whom he found amnesic of her past life and abandoned his quest. When the first mutant child was born at last, Beast helped with locating the child at the mansion. After the team set-up in San Francisco, the Skrulls invaded. Hank adapted the Legacy Virus to infect the Super-Skrulls and, without testing of an antidote, Cyclops decided to use it on them.

In order to save mutantkind from the effects of M-Day, Beast and Angel decided to gather a team of specialists, the X-Club. They gathered Madison Jeffries, Dr. Yuriko Takiguchi, Dr. Nemesis, and Dr. Kavita Rao. Beast and the X-Club traveled back to 1906, in order to find Dr. Nemesis's parents and discover the origins of modern mutation. During the mission, they also fought an early version of a Sentinel, created by the Hellfire Club, and inadvertently caused the San Francisco earthquake. However, when they returned to the present, they found that their DNA evidence had been buried beneath where the Dreaming Celestial was standing in the park. Dr. Yuriko Takiguchi died of natural causes, shortly after, and Beast spoke at his funeral. Cyclops then asked him to locate Cable and Hope in the timestream, as well as provide time machines to send a group of X-Men to aid them. Although Beast was unaware of the formation of X-Force, he warned Cyclops that he did not agree with the plan if they were to assassinate Bishop in the future and further protested when Cyclops pulled X-Force from a mission to save the lives of Boom-Boom, Hellion, and Surge.

After being arrested by H.A.M.M.E.R for protesting in San Fransisco, Beast became a test subject for the Omega Machine (designed by Dark Beast to eradicate mutant powers and place them in Weapon Omega), while being held prisoner along with Professor X on Alcatraz Island by Norman Osborn. Hank was tortured daily, until Cyclops sent Magik and X-Force to rescue the captive mutants. After they settled-in on Utopia, Beast informed Cyclops that he was quitting the X-Men. Cyclops begged him to stay, saying he needed Hank to tell him when he would go too far, to which Beast replied, "Scott, you've gone too far". Reed Richards took the liberty of assembling five of the eight smartest people on the planet, including Hank McCoy, Hank Pym, T'Challa, Amadeus Cho, and himself, to help analyze Bruce Banner's condition after becoming unable to change into the Hulk. McCoy ran DNA tests and reported no mutant or mutate cells in Banner's bloodstream.

The super-villain scientist cabal known as the Intelligencia plotted to kidnap the world's eight smartest people to remove their opposition. To this end, Red Ghost and his Super Apes captured Hank and T'Challa, while Reed, Doctor Doom, Pym, and Banner were captured by other means, Cho evaded capture, and Tony Stark was already brain-dead. Hank was one of the heroes gamma irradiated, but Banner released Beast, Mister Fantastic, Black Panther and Wasp to help him re-tool the Cathexis Ray Generator so that he could draw the gamma energy out of the heroes, and once restored as the Hulk, destroyed the Intelligencia Hellicarrier. Beast joined his girlfriend Abigail Brand as a member of S.W.O.R.D.. Not long after, he was made a fugitive by Henry Gyrich and returned to the X-Men to attend Nightcrawler's funeral and stayed on as a doctor, during Bastion's attack on Hope. Hank and Prodigy briefed the team about the timesphere Bastion was using to send the horde of over 170,000 Nimrods to Utopia and was instrumental in finding Bastion's timeline and attuning Cable's time-travel device. Hank tended to the wounded, when they returned, then, once again, left the team, despite Namor's insulting him as a deserter Beast returned to the Avengers, helping Steve Rogers with his team of Secret Avengers. The team first battled a resurrected Fu Manchu and the Shadow Council.

Beast sided with the Avengers in the battle against the X-Men and joined a group of Avengers on a mission to space to confront the Phoenix Force. Their mission fails however and the Phoenix arrives on the Moon to claim its host. An attack from Iron Man however breaks the Phoenix into five pieces which claim Cyclops, Emma Frost, Magik, Namor and Colossus as its hosts. The Phoenix Five go about making the Earth a better place to live by outlawing and stopping all wars, destroying weapons, providing free food, water and energy for everyone. The Avengers still plotted to stop them (sure that they would eventually lose control). Hank was initially opposed to this, but then witnessed Namor invade and nearly destroy Wakanda (this also brought Professor X to the Avengers' side). Hank then aided the Avengers in rescuing their captive members from Limbo, where Spider-Man tricked Colossus and Magik into defeating each other. This left only Cyclops and Emma remaining. After witnessing several atrocious acts by the remnants of the Phoenix Five, the remaining X-Men defected to the Avengers. In the final battle, Hank witnessed his longtime friend Cyclops murder Charles Xavier, and become a new Dark Phoenix. After Cyclops was defeated, Hope Summers took control of the Phoenix Force. She then used it to repopulate the mutant race, and dispersed the Force completely. Beast suffered a new mutation which seriously and slowly hurt him. He decided that if he were to die, he would try to show Cyclops how far he has fallen. Hank traveled to the past and gathered the five original X-Men and brought them to the present. Upon arrival, they rebelliously went on their own to meet the future Cyclops to see what he had become. Later with the help of himself from the past, Hank managed to overcome his mutation and survive.

After years of service with the Avengers (during which he also aided the X-Men against Dark Phoenix), the Beast took it upon himself to reorganize another super-hero group, the Defenders, into a more formal combat organization.