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Megatron is the leader of the Decepticons in the Transformers: Animated continuity and largely resembles other incarnations of the character. The most notable change from previous and subsequent versions is that he did not know Optimus Prime prior to the start of the series, and their antagonism throughout the series is not on the personal level found in other branches of the Transformers franchise.
Megatron has served as the leader of the Decepticons for an unknown period of time, and was the most feared combatant of the Great War, during which the most impressive Autobot action against him personally was that Ultra Magnus once dented his face (according to a tech spec). The rise of the Omega Sentinels, particularly Omega Supreme, resulted in the defeat of the Decepticon forces and their expulsion from Cybertron; driven to the edges of the galaxy, they disappeared so completely that many resulting generations of Autobots believed they were extinct. Megatron endured, however, having secured his flagship Nemesis, whose crew eventually came to include his treacherous underling Starscream, loyal minion Lugnut, the psychologically unstable Blitzwing, and the techno-organic female Decepticon Blackarachnia who was once the Autobot Elita One. Eventually they detected the AllSpark, the source of Cybertronian life that the Autobots had sent into space to keep it from Megatron so long ago, aboard the Autobot vessel commanded by Optimus Prime. Megatron flew into battle to recover the artifact himself, but between Starscream's treachery, the Autobots' unexpected abilities, and the ship being pulled through a nearby Space Bridge, he was heavily damaged, with parts of him crash-landing in the vicinity of Detroit on Earth.
Megatron's head and one severed hand were discovered by Isaac Sumdac, who used the technology he derived from them to build his company Sumdac Systems, with the two Cybertronian relics being moved into his private lab inside Sumdac Tower. After the Autobots were reawakened following decades in stasis and the AllSpark empowered a key belonging to Isaac's daughter Sari Sumdac, Megatron's head was revived by this device and learned of Starscream's treachery, which he had admitted during his recent battle with the Autobots under the belief that Megatron had perished. Vowing revenge on all of his enemies, Megatron turned his attention to deceiving Isaac Sumdac, convincing him that he was an Autobot who had been critically damaged and couldn't bear the thought of his "comrades" seeing him in such a state. This farce enabled Megatron to set about efforts to create a new body for himself, which had the unexpected result of creating four new Transformers: the three Dinobots and Soundwave, all of whom Megatron briefly attempted to manipulate to his advantage. He later established a private communications line with Lugnut in order to utilize him and Blitzwing in his schemes as well, but some of his activities began to stir Sumdac's suspicion as to his true motives.
Surprisingly, much of Megatron's body-his torso, one arm, and his legs-remained intact and were commandeered by mutated space barnacles, organisms that used them to menace the Autobots Prowl and Bumblebee before being defeated. This enabled Sumdac to recover the inert form and bring it back to Sumdac Tower, only for the Decepticons to arrive in the midst of his repair efforts and reveal Megatron's true identity to him. Starscream also learned of Megatron's continued existence, but due to Autobot interference and Megatron's own actions was unable to finish his hated leader off; Megatron then utilized Sari's key to repair and reformat himself into a new frame with the alternate mode of a VTOL helicopter. After punishing Starscream for his treachery and the Autobots for their opposition to his plans, he set his sights on recovering the AllSpark, and eventually managed to embed it in his chest. However, Optimus Prime was able to use the AllSpark Key's power to shatter the crystalline AllSpark, scattering it's fragments across the planet; Megatron was beaten, but retained Isaac Sumdac as a hostage.
Megatron forced Sumdac to create signal dampeners that would hide him and those Decepticons loyal to him from Autobot sensors, and then put him to work on an ambitious new project: building a Space Bridge that Megatron's forces could use to invade Cybertron. Additionally, Megatron contacted the Decepticon forces on the edge of the galaxy and instructed them to begin launching attacks against the Autobots in order to lure the Elite Guard away from Cybertron, with the intent being that all the Decepticons would then transport to the defenseless Cybertron via the commandeered Space Bridge network. He would be forced to contend with the continued presence of Optimus Prime's Autobots as well as the continued treachery of Starscream, who had been rendered immortal by a fragment of the AllSpark which had become embedded in his forehead. However, his forces would also benefit from the addition of the Constructicons, though for a time they were missing in action due to developing amnesia, and of reconnecting with his double agent Shockwave.
Eventually Megatron's grand plan was on the edge of fruition, but with Sumdac unable to complete the Space Bridge, he sought out Cybertron's foremost Space Bridge authority and discovered that it was none other than Bulkhead, a member of Optimus' crew. This led him to abduct the bulky Autobot and force him and Sumdac to complete the machine, only for his base to be attacked by Optimus Prime's forces joined by Elite Guardsmen Blurr and a force of clones created by Starscream. The clones would end up joining Megatron after Sumdac hijacked the Headmaster unit and took over Starscream's body, but Omega Supreme would then appear to attack the installation. The ensuing struggle saw the Space Bridge go critical and draw Megatron and Starscream's head through a portal into space, with Megatron confined by stasis cuffs.
Starscream's unexpected new powers enabled him to free Megatron, and the pair made their way onto Omega Supreme after the giant Autobot teleported into their vicinity and managed to take control of him. Megatron soon took the robot back to Earth to attack the Autobots, only for Prowl to interfere and disrupt his control. Starscream then seized control of the giant Transformer, but was thwarted when the Autobots sent Omega Supreme randomly teleporting around the galaxy. Megatron was eventually able to halt this, and succeeded in rescuing Lugnut after his loyal brute was left adrift in space; subsequently, Megatron relocated Omega Supreme to the skies above Cybertron. They eventually departed, but not before adding Shockwave to their growing crew and taking the Autobot Arcee captive.
Megatron took his forces back to Earth's solar system and landed on the moon, where they used Protoforms stolen from Yoketron and the wreckage of the Nemesis to construct mindless clones of Omega Supreme. Megatron soon unleashed them upon Earth after dismissing the still traitorous Starscream, and was engaged by Optimus Prime's forces, with Optimus employing a flight pack and the might Magnus Hammer. He was thus able to halt one of the Lugnut Supremes, and Megatron unleashed the others only for them to fall under Starscream's control. Fitted with explosives, the monstrous titans prepared to destroy Detroit, only for Omega Supreme-whom the Autobots had recovered-to destroy one of them, while the other's explosion was contained by AllSpark energy harnessed by Prowl and Jazz. Megatron was trapped within this explosive radius, but by some means-hinted by Transformers: The AllSpark Alamanc to be his own prior union with the AllSpark-Megatron survived.
The leader of the Decepticons attacked Optimus but was then defeated, and then invited his rival to finish him off. However, Optimus refused to allow Megatron to escape judgement, and took him into custody instead. Along with his captured subordinates, Megatron was then taken back to Cybertron in chains.
Megatron was subsequently interred in Trypticon Prison, and an effort to liberate him was late made by the Stunticons.