In 1983 he worked in a restaurant while he searched for publishers for his comics. He met a waitress who was attending the University of Massachusetts Amherst and followed her to Northampton, Massachusetts. While searching for a local underground newspaper to publish his work, he began a professional relationship with Peter Laird, who worked at nearby Dover, New Hampshire, and the two collaborated for a short time on various comics projects.

In May 1984, Eastman and Laird self-published the first black & white issue of Teenage Mutant Ninja Turtles. The forty-page oversized comic had an initial print run of 3,275 copies and was largely funded by a US$1000 loan from Eastman’s uncle Quentin. It was published by the duo’s Mirage Studios, a name chosen because, as Eastman says, “there wasn’t an actual studio, only kitchen tables and couches with lap boards.” By September 1985, their first issue had received three additional printings.

The Turtles phenomenon saw the duo invited to their first comics convention at the tenth annual Atlanta Fantasy Fair in 1984, where they mingled with notable comic creators like Larry Niven, Forrest J Ackerman and Fred Hembeck.

Eastman purchased his first piece of original artwork (“a couple of pages that were penciled by Michael Golden and inked by Bob McLeod for Marvel Comics’ Howard the Duck”) at the Atlanta Fantasy Fair, the convention he and Laird attended in 1984. Collecting subsequently became “quite an addiction” for him, and combined with his experiences in getting his, and others’, comics work recognised as “Art,” led to him founding the Words & Pictures Museum, which operated as a brick-and-mortar museum from 1992–1999.

Their fifth issue of Teenage Mutant Ninja Turtles was released in November 1985, and was downsized to the more common American comics-format and size. The previous four issues were also reprinted in this size and format with new colored covers. Also in 1985, Solson Publications released How to Draw Eastman and Laird’s Teenage Mutant Ninja Turtles. Solson would follow this up with the six-issue Teenage Mutant Ninja Turtles Authorized Martial Arts Training Manual as well as one issue of Teenage Mutant Ninja Turtles Teach Karate volume in 1987.

Palladium’s role-playing game brought the Turtles to the attention of licensing agent Mark Freedman and the Turtles phenomenon took off, with the various characters soon appearing on T-shirts, Halloween masks, mugs, and other paraphernalia. A five-part televised cartoon mini-series based on the Turtles debuted in December 1987. The half-hour episodes were produced by Osamu Yoshioka and the animation was directed by Yoshikatsu Kasai from scripts David Wise and Patti Howeth. The mini-series was successful, leading to a full series, with the mini-series forming the first season. The series had a 9-year, 10-season, 193-episode run. Bob Burden writes:

In January 1988, Eastman and Laird visited Playmates Toys, who wished to market action figures based on the comic book and animated cartoon series, further cementing the Turtles’ place in history and making Eastman and Laird extremely successful.

Eastman founded Tundra Publishing in 1990, to realize personal and other projects. He joined with other comic creators like Scott McCloud and Dave Sim to form the Creator’s Bill of Rights. Eastman felt obligated to expand it beyond theory and into practice, providing a forum for comics creators to work for a publisher while maintaining ownership of their work.

Eastman has acted in a small number of films, including Guns of El Chupacabra in 1997 and The Rock n’ Roll Cops in 2003. He also had a supporting role in the 2004 Troma film Tales from the Crapper. Before that, he had a cameo in the 2000 sequel to The Toxic Avenger called Citizen Toxie: The Toxic Avenger IV. and had a small role in the first TMNT movie as a garbage collector.

On June 1, 2000 Laird and the Mirage Group purchased Eastman’s ownership in the Teenage Mutant Ninja Turtles property and corporations. Eastman wanted to move on to other projects. The buyout was completed on March 1, 2008.

Creative differences began to strain Eastman and Laird’s partnership. In an interview in 2002, Laird noted that the two hadn’t spent much time together since 1993. Eastman moved to California while Laird stayed in Massachusetts.

In 2011, Eastman began working with the TMNT series again as a writer and artist on the IDW comic series, as well as an adviser on the 2014 reboot of the Teenage Mutant Ninja Turtles film series. Eastman is said to have a cameo in the film as a doctor, and has voiced the character Ice Cream Kitty in the 2012 CGI series.

Eastman sold the magazine to digital and music veteran David Boxenbaum and film producer Jeff Krelitz in January 2014. Eastman will continue to serve as publisher of the magazine, and is a minority investor in the new Heavy Metal.

In December 2019, issue #100 of IDW Publishing’s Teenage Mutant Ninja Turtles comic series featured a teaser ad for an upcoming comic project titled The Last Ronin in which the prospect of a possible reunion and cooperation between Eastman and Laird was held out. The project was confirmed in April 2020, with a TBD release date sometime in the summer.