Unicron's one weakness is the Creation Matrix, the essence of the light god Primus. When the universe was in its infancy the two fought as energy beings until Primus, to save the life that was being wiped out as they fought, tricked his enemy and trapped both their essences in barren lumps of space debris. Over billions of years Unicron psionically reshaped his prison into its current form, while Primus became the planet Cybertron, creating the first Autobots to one day fight Unicron and safeguard the universe.
Unicron learnt of Cybertron's location in 1990 when Primus was awoken by accident. He arrived in 1991, and the combined forces of Optimus Prime and Scorponok were unable to stop him. Only when the tainted Matrix was cleansed by Optimus Prime could it be opened within the planet-devourer and destroy him.
In the future, a future that may yet come to pass [provided a lot happens between the end of Marvel's G2 and the year 2005] Unicron returned. At this time, Optimus Prime was dead, and Megatron floated through space near death. Unicron reshaped the Decepticon leader into Galvatron. But, thanks in part to Galvatron betraying his new master, the Autobot Hot Rod inherited the Matrix and managed to open it inside of Unicron, becoming the new Autobot leader Rodimus Prime in the process. Unicron's physical form was again demolished, with the exception of his head.
Unicron directed his robotic head to crash-land on the planet Junk, where he enslaved the Junkion inhabitants using his mind-control powers, forcing them to rebuild him. He had Death's Head assassinate Shockwave and replace him with his own puppets, Cyclonus and Scourge. At his command, they started an all-out war on Cybertron, where there had previously been a stalemate. Rodimus Prime learnt of Unicron's presence on Junk, travelled there, and trapped his essence within the Matrix as Wreck Gar destroyed his partially completed body with explosives. Cyclonus and Scourge were sent back in time several hundred years, and came under the command of Scorponok.
On return from the "Time Wars" of 1989/2009, Rodimus's group of Autobots found themselves in an alternate future where Galvatron had never gone back in time, and now ruled Cybertron. While they were in this reality Unicron possessed Rodimus, within whom he and the Matrix now resided, and caused severe Autobot casualties before his influence was cut off.
In 2010, on Cybertron, Unicron repeated this trick. This time Rodimus himself took on the appearance of Unicron. Great devastation and many deaths resulted before Prime could reassert control once more.
In 2356, the tainted Matrix made Rodimus Prime grow weak and Unicron
started influencing him more subtlely. In 2510 the Autobots began fighting
and killing each other following a massive victory over the Decepticons.
Unicron's handiwork could not be ruled out.