The Big Guy is decommissioned in favor of Quark Industries' newest creation, Rusty the Boy Robot. But when an alien Annihilator threatens to destroy New Tronic City, it's clear that Rusty is not quite ready for prime time. The Big Guy is reassembled and joins the fight along with Rusty. General Thorton orders that the temporary alliance become a permanent partnership.

A telepathy experiment goes awry and a Quark Scientist, Dr. Neugog, is transformed into a giant brain on spidery legs. Neugog uses his telepathic powers to drain the minds of the world's greatest scientists. Meanwhile, Dr. Slate accidentally discovers that there's a man in the Big Guy suit.

Rusty tags along with Dwayne to his nephew's birthday party. Rusty's present is a piece of stolen alien technology, known as a Dimetrium Agglomerator. The aliens, Emek and Naard, own the Agglomerator and come to claim it.

Dr. Gilder, the Legion Ex Machina's mole within Quark, has developed a personal grudge against Donovan, so he takes control of a prototype and tries to assassinate him. Donovan is taken to the S.S. Dark Horse for his own safety. Gilder then hacks into Rusty, gives him a ""big gun"", and sets out to destroy Donovan.

Dr. Slate, Big Guy and Rusty find out that the Legion Ex Machina's mysterious ""final assembly"" is taking place in a network of underground tunnels. When Big Guy and Rusty find the tunnels, they derail a robotic train. Inside the massive train's cargo hold is a gigantic hand that boasts a built-in high-tech cannon. With their plan uncovered, the Legion Ex Machina members decide to activate their latest creation ahead of schedule and missing a hand.