Pullman was born in Hornell, New York, the son of James Pullman, a physician, and his wife Johanna (née Blaas), a nurse.
After graduating from Hornell High School in 1971, he attended the State University of New York at Delhi (SUNY Delhi) and the State University of New York at Oneonta in the 1970s. He eventually received his Masters of Fine Arts degree from the University of Massachusetts Amherst. Pullman taught theater at SUNY Delhi and Montana State University's School of Film and Photography, where he was persuaded by his students to attempt film.
During the 1980s, he primarily worked with theater companies around New York and Los Angeles. His first prominent film role was in Ruthless People (which starred Danny DeVito and Bette Midler). Other notable films included the lead in Spaceballs (1987), The Serpent and the Rainbow (with Zakes Mokae), and While You Were Sleeping (1995). In 1996, he played the president of the United States in the sci-fi disaster film Independence Day. A year later he had a major role in Lost Highway (1997) and voiced Korso in the animated post-apocalyptic film Titan A.E.. His more recent films have included The Grudge and Scary Movie 4.
From February 2001 until February 2002, Pullman starred with Mercedes Ruehl, in Edward Albee's play The Goat, or Who is Sylvia? on Broadway. The play won several awards: 2002 Tony Award for Best Play; 2002 Drama Desk Award Outstanding New Play; 2003 Pulitzer Prize for Drama. Pullman was nominated for the 2002 Drama Desk Award Outstanding Actor in a Play. He starred as Dr. Richard Massey in the miniseries Revelations. Pullman starred in Edward Albee's Peter and Jerry, at Off-Broadway's Second Stage Theatre in New York. For his performance, Pullman received a second Drama Desk Award nomination for Outstanding Actor in a Play in 2008.
In addition to acting, Pullman is a creative writer. His first play, Expedition 6, is about the International Space Station mission Expedition 6 that was in orbit at the time that the Space Shuttle Columbia was destroyed on reentry, grounding the U.S. space shuttle program, which was to provide the vehicle for the crew's return to earth. The play opened at San Francisco's Magic Theater in September 2007.
He also appeared in the Broadway production of David Mamet's Oleanna, co-starring Julia Stiles. The production opened at the John Golden Theatre October 11, 2009, and closed on December 6, 2009, playing 65 performances.
He is also a Jury Member for the digital studio Filmaka, a platform for undiscovered filmmakers to show their work to industry professionals.
Pullman played Oswald Danes, a pedophile and child killer, in Torchwood: Miracle Day, the fourth series of the BBC/Starz Entertainment television show Torchwood (which was originally a spinoff to BBC's runaway hit series Doctor Who), the former of which began airing in July 2011. For his performance as Danes, Pullman has received a Saturn Award nomination for Best Supporting Actor In Television.
From 2012-13, Pullman portrayed the President of the United States in the television comedy series 1600 Penn.
Beginning August 2, 2017, the USA Network began airing its new eight-episode, limited-series-format murder mystery The Sinner. Pullman plays Detective Harry Ambrose, who is trying to figure why the already-confessed murderer, Cora Tannetti (series star and execute producer Jessica Biel), would suddenly stand up and murder an apparent complete stranger, on a beach full of witnesses to the heinous event.
Pullman is married to Tamara Hurwitz, a modern dancer, and they have three children. Hurwitz is of part Norwegian descent. At the age of 21, Pullman suffered a head injury and lost his sense of smell. He co-owns a cattle ranch with his brother in Montana, near the town of Whitehall, where he lives part-time. He also serves on the Board of Trustees at Alfred University and was awarded an honorary doctorate on May 14, 2011.