In 2008, he appeared in the comedy film Forgetting Sarah Marshall which stars Jason Segel and Kristen Bell, as Detective Hunter Rush.
In February 2010, audiences got to hear his first time playing Batman in Justice League: Crisis on Two Earths, a loose adaptation of Grant Morrison's JLA: Earth 2 story. Willam van der Woodsen, father of Serena and Eric van der Woodsen, on the third and fourth seasons of Gossip Girl.
On June 1, 2011, Baldwin starred in the indie film Sexy Evil Genius, alongside Seth Green, Harold Perrineau Jr., Katee Sackhoff and Michelle Trachtenberg. In July 2011, Baldwin joined the CBS drama Hawaii Five-0 for a multi-episode arc.
On March 22, 2012, Baldwin guest starred on the NBC show 30 Rock.
In 2011, Baldwin starred in the Lifetime Original Movie, The Craigslist Killer which aired January 3, 2011.
He plays the lead detective on the case of the killer, Philip Markoff, who connected with victims through Craigslist ads placed in Boston, Massachusetts.
Baldwin was also featured with his brother Daniel in Uni Globe Entertainment's breast cancer docu-drama, 1 a Minute.
Acccording to most biographies on the Baldwin Brothers, William and his brothers, Alec Baldwin, Stephen Baldwin and Daniel Baldwin, attended Massapequa High School, but they actually went to Alfred G.
Baldwin was raised in a Catholic family, and has English, Irish, Scottish, French-Canadian, and German ancestry. Before starting his acting career, Baldwin was a fashion model for Calvin Klein.
His first starring role was in a TV movie as Robert Chambers, alongside Danny Aiello and Lara Flynn Boyle in The Preppie Murder, which aired on ABC in 1989.
Baldwin plays Lance Drake Mandrell, an actor who plays Jack Donaghy – the role played in the series by Baldwin's real-life brother Alec – in a made-for-TV movie within the show. Baldwin appeared in the fourth and final season of Wilfred, replacing Dwight Yoakam in the role of Bruce.
In 2015, he narrated for the documentary A Wing and a Prayer, a film about American fighter pilots who assisted in the 1948 Arab–Israeli War and the founding of the Israeli Air Force.