After attempting to create a growth formula that will enlarge plants to help feed starving nations, the scientist again is unsuccessful and pours the remnants of his project into Chemo, finally filling the massive vessel. These chemicals cause a massive reaction that results in Chemo coming to life and growing into a building-sized giant. Chemo proceeds to poison the scientist with a lethal dose of the growth-formula chemicals, and then goes on a rampage, only to be defeated by the robotic Metal Men.
Chemo proves to be an impressively resilient monster. It is apparently incapable of being killed. It returns time and time again, undergoing various resurrections and mutations, and has several more encounters with the Metal Men as well as squaring off against Superman more than once. During the Crisis on Infinite Earths, Brainiac and Lex Luthor use Chemo as a living weapon stationed on Earth-4. Chemo proceeds to destroy much of that earth's New York City and kills Aquagirl by spewing more than a dozen varieties of corrosive acids into the ocean. It is finally destroyed when Negative Woman uses her energy powers to shatter Chemo's living plastic shell.
After the Crisis, Chemo is resurrected and fights against a variety of superheroes, including its old enemies the Metal Men, Superman, and Supergirl. It has also fought with Superman as part of the Suicide Squad formed by President Lex Luthor to break Doomsday out of his prison at the JLA Watchtower teleporters.
The Society has the Brotherhood of Evil acquire Chemo and they used Chemo as a living chemical weapon by dropping him onto the city of Blüdhaven, killing hundreds of thousands of people. Dick Grayson (Nightwing) had agreed with Deathstroke for the 72 hours of ceasefire in Blüdhaven in exchange for staying away from Rose. However, Chemo is dropped before the 34th hour. Chemo bathes the entire city in radiation and toxic waste. All able-bodied superheroes attempt to save the infected, but Chemo quickly reforms itself. Superman battles the monster with the plan that he would regenerate quicker as the battle ensued. While Chemo regenerates, he continues to suck the toxins and radiation out of the city, cleansing the city of the remaining radiation and waste. In the end, Superman lifts Chemo and throws him into outer space.
On the cover of Justice League of America (vol. 2) #13, it shows Chemo as a member of the latest Injustice League.Joker and Gorilla Grodd use Chemo to destroy a burrowing Kraken-like creature that attacks the villains.
A promo for the original pilot episode (viewable on disc four of the Justice League Season 1 box set, ), briefly features Chemo battling the Martian Manhunter.