After three years of graduate school, Cohen took a leave of absence and started writing sample TV scripts. In 1992, this landed him a job writing two of the earliest Beavis and Butt-Head episodes. In 1993, Cohen began working on The Simpsons, writing or co-writing thirteen episodes. Nearly five years later, Cohen would team with Matt Groening to develop Futurama, where he served as writer or co-writer of seven episodes and executive producer and head writer of the series’ entire run. Cohen has won four Primetime Emmy Awards: Two for Futurama and two for The Simpsons.

Cohen co-developed Futurama, along with The Simpsons creator Matt Groening. Cohen served as head writer, executive producer, and voice director of the series. He was also the voice director of the Futurama video game. After spending a few years researching science fiction, Groening got together with Cohen in 1997 and developed Futurama, an animated series about life in the year 3000. By the time they pitched the series to Fox in April 1998, Groening and Cohen had composed many characters and storylines; Groening claimed they had “gone overboard” in their discussions. Groening described trying to get the show on the air as “by far the worst experience of [his] grown-up life”. The show premiered on March 28, 1999.

When the FOX primetime animated shows unionized in 1998, Cohen was forced to use a different name for professional purposes as there was already another member credited as David S. Cohen and the Writers Guild of America does not allow members to use the same name for onscreen credits. Instead of using his full middle name, he chose to use the middle initial “X”—because it sounded “sci-fi-ish”—and has jokingly said that the “X” would make him “the David Cohen people would remember”. The “X” does not actually stand for anything, but Cohen included a period “so people don’t think it’s some mathematical formula: ‘David times Cohen’ or something”.

Cohen told Newsday in August 2009 that the reported 26-episode order means “[i]t will be up to 26. I can’t guarantee it will be 26. But I think there’s a pretty good chance it’ll be exactly 26. Fox has been a little bit cagey about it, even internally. But nobody’s too concerned. We’re plunging ahead.” Two episodes were in the process of being voice-recorded at that time, with an additional “six scripts … in the works, ranging in scale from ‘it’s a crazy idea that someone’s grandmother thought of’ to ‘it’s all on paper’. …”The first episode is tentatively titled ‘Rebirth’ — and in a surprisingly literal fashion, as things turn out”. It aired June 24 on Comedy Central.