He planned to be a scriptwriter from an early age, but a college lecturer discouraged him, and Piller started out in television working as an Emmy Award-winning journalist for CBS News in New York, WBTV in Charlotte, North Carolina, and WBBM-TV in Chicago, Illinois.

However, he then moved to Los Angeles, California and the entertainment side of television in the late 1970s, working as a censor and then a programming executive for CBS.

Piller attended the University of North Carolina at Chapel Hill, where he was a member of the Pi Lambda Phi fraternity.

When Wagner dropped out of leading the writing staff for the show's third year, Piller was invited to assume the showrunner position, reporting to executive producer Rick Berman, as of the fifth episode of the third season, "The Bonding".

Star Trek: Deep Space Nine debuted in January 1993 with "Emissary", the pilot episode written by Piller, to the highest-ever ratings for a syndicated series premiere.

Piller continued as a creative consultant on Deep Space Nine and Voyager, sending in notes on scripts as they were being prepared for production.

[12] She described in an interview in 2013 that the studio was surprised by his honesty about the writing process and production of Insurrection and paraphrased the response of the executives at Paramount Pictures, saying, "We can't let the public know what we do here; what goes on behind the scenes!

The WB ordered scripts for all four productions,[14] and looked to be moving ahead with Day One, a post-apocalyptic serial based on the UK television mini-series The Last Train.

The series, co-developed with Shawn and starring Anthony Michael Hall and Deep Space Nine's Nicole de Boer, debuted June 16, 2002 on USA Network with 6.4 million viewers, the biggest premiere ever on that channel.

He was teacher, mentor, and guide to so many Star Trek writers that it can truly be said that he imprinted ST story telling in a way that will endure forever.

Full page tributes to him were published in Variety and The Hollywood Reporter, while Lions Gate Television put out a press release describing him as, "an extraordinary storyteller and cherished friend, who inspired all of us who knew him.

[17] He has been subsequently credited with giving The Next Generation its "soul" by Star Trek writer Paula Block, while Terry J. Erdmann felt that the complex characters of Deep Space Nine were entirely formed from Piller's imagination.

[17] Likewise, TNG cast member Wil Wheaton said that Piller was "more responsible than anyone else for Next Generation transforming itself into the amazing show it became in season four".