Most of the original E-100 Series were put to little use prior to being destroyed. The original line-up of E-100s were first put into a competition with each other to retrieve Froggy who had absorbed Chaos' tail. Gamma located Froggy at Big the Cat's hut, knocked the feline over and captured the frog. When he returned, Eggman was delighted to see Gamma's success, while the other E-100s had all failed and brought back regular frogs. With Gamma as the victor, Eggman placed the other E-100s at various outposts assigned Gamma to his next mission: retrieving a Flicky from Amy Rose.
After Gamma freed Amy from her prison, he was called up to the deck to dispose of the trespassing Sonic and Tails. A grueling battle ensued, but Gamma was ultimately defeated by Sonic. Before he could be destroyed however, Amy got between the two and informed Sonic that Gamma had helped her escape. Hearing this, Sonic left the robot alone, and Sonic, Amy, Tails and Gamma all fled the descending Egg Carrier.
Gamma then set about destroying any of the other E-100 units he could find and when he'd destroyed them all, he went on to fight the Eggman Empire. Robots similar in appearance to Gamma were made to guard Eggman's pyramid base.
Dr. Eggman employed a series of E-105 robots as an army to invade Feral Forest. These robots were very unsuccessful, as the local villagers along with Sonic the Hedgehog, Sally Acorn, Geoffrey St. John and Hershey Cat managed to destroy the entire E-105 army with relative ease.
Robots similar to the E-Series were also seen among the robots sent to the ruins of Robotropolis with the intention of breaching its force-field and allowing nuclear waste to spread to Knothole. Like the other robots, they were also repelled by an all-out assault led by Knuckles the Echidna, Amy Rose, Rouge the Bat, and General Armand D'Coolette.
After Gamma was believed by Eggman to be too much of a threat, he had an E-100 unit called E-123 Omega that had been left in storage track down the rogue Gamma, but the Guardian Units of the Nation wished to have Gamma as an agent of theirs and also wished to offer the old robot help. In order to do so, they sent Shadow the Hedgehog out to find him. Omega was successful in his mission, but before Gamma was destroyed, he uploaded his free will into Omega, prompting him to join the Guardian Units of Nations and fight the Eggman Empire in his "brother's" footsteps. With Gamma destroyed, Omega is now the last known unit of the E-100 Series.