As a contributing Writer, Fuller's work has been featured on several shows, including Star Trek: Voyager and Star Trek: Deep Space Nine, earning twenty-two episode writing credits for the Star Trek franchise. Fuller is himself a fan of science fiction, and in an interview said that his favorite Star Trek series were the 1960s original, followed by Deep Space Nine, The Next Generation and Voyager. Fuller has called DS9 his favorite spin-off, stating: "There were lots of new and innovative things going on during Deep Space Nine and that's why it's my favorite of the new series'. It was much more character-based". Fuller worked on the DS9 episodes "The Darkness and the Light" and "Empok Nor".

Fuller wrote the teleplay for the 2002 adaptation of Carrie, based on the novel of the same name by Stephen King. Next, he created Dead Like Me which ran on Showtime for two seasons from 2003 to 2004, although Fuller left early into the first season. He then co-created Wonderfalls with Todd Holland, which ran on Fox in 2004, with only four episodes being aired and the rest premiering on DVD. Near the end of 2004, Fuller got a pilot commitment from NBC for The Assistants, although the show never got past the script stage. In 2005, Fuller wrote the pilot to the animated comedy The Amazing Screw-On Head for the Sci Fi Channel, which aired in 2006 but was not picked up for a series. He next worked on NBC series Heroes, where he joined as a consulting Producer after the pilot and became a co-executive Producer for the first season. He also wrote a couple episodes for Heroes, including "Company Man" which TV Guide named one of the 100 greatest episodes in television history.

Next he created Pushing Daisies, about a pie-maker (Lee Pace) who can bring dead things back to life temporarily, debuted on ABC on October 3, 2007. On July 17, 2008 the show was nominated for twelve Emmy Awards from the Academy of Television Arts & Sciences, including one for Fuller for Outstanding Writing of a Comedy Series. It ultimately won seven Emmy Awards: for Best Supporting Actress (Kristin Chenoweth), Best Art Direction, Best Costume, Best Music, Best Make-Up, Best Editing, and Best Direction of a Comedy Series (Barry Sonnenfeld). The second season of Pushing Daisies began October 1, 2008 on ABC. In mid-November, ABC announced that it would not order new episodes for season two after the 13th. The series's final episode aired on June 13, 2009.

Fuller's next project was the Hannibal Lecter series Hannibal, which premiered on NBC in 2013, and renewed for a second season in 2014. Fuller had developed High Moon for Syfy, based on the book The Lotus Caves, which filmed a pilot in late 2013, but was not given a series order.

In July 2014, it was announced that Starz had acquired the airing rights to the novel American Gods, and that Fuller, with Producer Michael Green, would develop the novel into a television series. The show premiered April 30, 2017, to critical acclaim. The show was renewed for a second season, but Fuller and Green left the show due to budgetary issues during the writing stage of the second season. As of early 2018, Fuller is working on a TV adaptation of The Vampire Chronicles, the novel series by Anne Rice.