After rival Marvel Comics acquired the rights, Infantino asked Jack Kirby for a series with a similar concept.

Later issues were written by Paul Levitz, Dennis O'Neil, David Anthony Kraft, Elliot S. Maggin, and Jack C. Harris (alternating), with art by Pablo Marcos, Keith Giffen, and Dick Ayers.

The only explicit connection to the DC Universe occurs in issue #29, in which Kamandi discovers a group of apes who worship Superman.

[10] Issues #49–50 of the series establish Kamandi's grandfather to be Buddy Blank, the former OMAC, and features a brief return of his satellite ally Brother Eye.

[13][17] A young Kamandi and his grandfather Buddy Blank appear in Countdown to Final Crisis, which sees the beginning stages of the Great Disaster as a virus causes humans and animals to develop aspects of each other.

[20] Writers on the series included Dan Abnett, Peter Tomasi, Jimmy Palmiotti, James Tynion IV, Bill Willingham, Steve Orlando, Marguerite Bennett, Keith Giffen, Tom King, Greg Pak, Rob Williams and Gail Simone while artists were Dale Eaglesham, Neal Adams, Amanda Conner, Carlos D'Anda, Ivan Reis, Philip Tan, Dan Jurgens, Steve Rude, Kevin Eastman, Joe Prado, Walter Simonson and Ryan Sook.

By Kamandi's time, an unspecified period after the Great Disaster, the effects of radiation and the intelligence-enhancing drug Cortexin cause various animals to become anthropomorphic.

He soon discovers that the only other intelligent humans left on Earth are Ben Boxer and his friends Steve and Renzi, a trio of genetically engineered mutants.

He also makes a number of animal friends including the dog scientist Dr. Canus, the tiger king Caesar, and his son Tuftan.

Later additions to the cast include the alien Pyra, the primitive girl Flower, her twin sister Spirit, detective Mylock Bloodstalker, and his associate Doile.