1000 years ago, give or take, as a protracted civil war between the Autobots and Decepticons came to an end on Cybertron when the former left the planet. The Decepticons were unable to pursue them due to the arrival of Gozer from its temple atop one a building. Shockwave, Starscream, Megatron, and Soundwave approached the Temple of Gozer. Gozer announced "The Traveler has come." Megatron demanded it to explain itself or face his wrath. Shockwave warned against antagonizing it and cautioned against its power was beyond his sensors' ability to categorize. Starscream had enough of their inaction and fired at Gozer. Gozer blocked his attack with its right hand then countered with lightning. Megatron berated Starscream. Soundwave suggested broadcasting a distress beacon. Starscream thought the Decepticons should have fled the planet, too. Megatron stated they did not flee and declared he would deal with Gozer himself. Megatron walked up the temple stairs. Vinz Clortho charged and leaped at him. Megatron knocked him aside. Megatron walked up to Gozer and asked why it came to his world. Gozer replied to came to end Cybertron and implored him to choose. Megatron didn't understand. Gozer explained it was time to choose the form of their destruction then quickly stated it was done. Starscream became worried. Shockwave asked him what he did. Starscream claimed he did nothing but had a fleeting thought about how he could be mighty enough to destroy the planet. Gozer's Destructor form manifested, a larger version of Starscream. Megatron shot Starscream in the right shoulder. He vowed he would pay for his indiscretion then ordered the alarm to be sounded. The other Decepticons rallied to them but it was not enough
The Decepticons battled Megascream and endured death on a scale they never experienced before. Shockwave stated their greatest weapons had failed. Starscream declared Cybertron was lost. Megatron smacked him and refused to accept that outcome. He still blamed Starscream for their predicament and explained he didn't fight to liberate Cybertron from Autobots just to see it fall to a god. Kremzeek appeared to them and stated destruction was always assured when Gozer the Traveler came. Kremzeek offered a way to escape. Shockwave countered with a strategic retreat as the more logical course of action. Soundwave pointed out the Decepticons' long-range vessels were already destroyed and thus, escape was unlikely. Shockwave conceded they should hear the offer out. Megatron yelled they weren't cowards. Shockwave asserted their extinction served no purpose and asked Megatron if his pride demanded the end of them all. Megatron was silent then told Kremzeek to tell them what his offer would cost. Kremzeek promised to deliver them from Gozer's wrath but at a high price. With no other choice other than destruction, Megatron accepted. Kremzeek destroyed Megatron's body. Starscream prematurely celebrated the end of Megatron and failed to see he was actually converted into a ghost. He aimed at Starscream. Shockwave and Soundwave were converted into ghosts next. Instead of pledging servitude, and aid in securing the Allspark, Megatron, Shockwave, and Soundwave turned on Kremzeek and surrounded him. Insulted by their refusal, Kremzeek absorbed them. Cybertron was destroyed by Gozer.
A thousand years later, the dispersal of Kremzeek at the Grosbeak Generating Station freed Megatron, Shockwave, Soundwave, and Starscream. Megatron vowed to destroy Optimus once and for all. Optimus instead brought up Starscream's request to help find new bodies and extended an offer of similar aid to them. He tried to tell Megatron the war was over. Megatron stated the war wasn't over until he destroyed him. Optimus declared he didn't want to fight. He disconnected his Proton Pack from his Ion Blaster. Megatron called him a coward. Optimus plugged the pack cord directly into his right wrist then stated he was just tired of war but wasn't afraid of no ghost. He generated a Proton Axe. Optimus and Megatron continued to battle each other. Megatron proclaimed he would die. Optimus retorted he would someday. Optimus slashed Megatron's chest. Megatron noticed the other Decepticons were just hovering. He ordered them to destroy Ectotron but Shockwave spoke up and declined to Megatron's surprise. Shockwave explained Optimus' offer was agreeable and it was only logical for them to work with the Autobots to restore their physical forms but emphasized they would still follow him if he had to strength to win. Soundwave added it was not in their best interests to hasten Autobot destruction. Megatron vowed he would deal with them when he was done with Optimus and they would regret their decision. Megatron fired but Optimus dodged the blast. Optimus implored Megatron to listen to the others because they just wanted to help him. Megatron extended his left arm and slapped Optimus then stated his help was worthless. He claimed the Decepticons died on Cybertron because of the Autobots' cowardice. Optimus denied it. He dodged Megatron and still pleaded with him. Megatron told him to help by joining him in death. He produced a ball and chain construct and attacked. Optimus decked him with an uppercut and stated times have changed and they needed to evolve but Megatron fell on Ectotron and inadvertently possessed him.
Megatron shot Optimus' left shoulder with the Particle Thrower. Megatron was pleased with his "evolution" and took joy in the tactile sensation of beating Optimus into oblivion. He lifted Optimus over his head and gloated. Peter elected to use a small canister of Psychomagnotheric Slime and yelled at Optimus to try to get Ectotron on his back. Megatron lifted Ectotron's right foot to stomp and stated there was no "try," was only success or failure, and the rest was meaningless struggle. Optimus caught Ectotron's foot and flipped him. Optimus disagreed and believed struggling was how success was learned. Peter was amused pop psychology made it into space. Ray instructed Optimus to hold Ectotron down. Optimus suggested he hurry as Ectotron seemed stronger. Ray joked he was fighting for two then climbed atop Ectotron's chest and poured the Psychomagnotheric Slime down his mouth. Megatron was ejected in a stream of Energon. Egon checked his P.K.E. Meter and alerted everyone of Megatron's re-manifestation.
Megatron appeared in a new form and admitted he was blinded by rage and realized how short sighted he was being. He revealed a new plan: possess Optimus Prime and conquer whole worlds. Megatron rushed towards Optimus but Ectotron wrangled him at the last second. He paused and asked Ray for a Trap. Once Megatron was trapped, the P.K.E. smoke dissipated and day returned. Peter predicted Optimus wanted to step on the Trap. Optimus admitted it crossed his mind. Peter asked if he wanted them to deposit the traps in their Containment Unit or something else. Optimus decided to take the three Traps with him, get them new bodies, and attempt rehabilitation. Peter was skeptical. Ray noted freedom was the right of all sentient beings. Optimus felt deja vu and speculated they could learn a lot from the Decepticons and help all be one again. Ectotron asked him if he really thought Megatron could be rehabilitated. Optimus stated he would always hope then admitted it was an interesting experience that would be long remembered.
- Megatron was prominently voiced by Frank Welker in many Transformers animated series and films. Welker had provided numerous voices for the Ghostbusters franchise, most prominently Ray Stantz and Slimer in The Real Ghostbusters.
- Megatron appears on the Fan Expo Dallas Cover of Transformers/Ghostbusters Issue #1.
- On page 6 of Transformers/Ghostbusters Issue #1, Megatron's reaction about someone choosing a Destructor Form mirrors Peter Venkman's in the first movie.
- On page 7 of Transformers/Ghostbusters Issue #1, Megascream's necklace bears the head of Megatron.
- On page 11 of Transformers/Ghostbusters Issue #2, the offer made by Kremzeek and what happens next mirrors a similar outcome in Transformers: The Movie in which Megatron, on the verge of death is made an offer by Unicron. Despite being prideful at first, Megatron accepts the deal. In exchange for becoming enslaved to the more powerful being, Megatron cheats death and is given a new form.
- On page 13 of Transformers/Ghostbusters Issue #2, the visual of Megatron's body crumbling was also seen in Transformers: The Movie.
- On page 8 of Transformers/Ghostbusters Issue #5, Megatron's mace is a nod to the Energon mace he employs against Optimus in the Transformers episode "More Than Meets The Eye, Part 2".
- On page 9 of Transformers/Ghostbusters Issue #5, the split image of Megatron's internal gears is from Transformers: The Movie when he is converted into Galvatron by Unicron.
- On page 12 of Transformers/Ghostbusters Issue #5, Megatron's "There is no trying" and Peter's quip is a nod to Yoda from Star Wars.
- On page 15 of Transformers/Ghostbusters Issue #5:
- Megatron appears on the Transformers Generations Ectotron Ecto-1 Cover of Transformers/Ghostbusters Issue #1.