Facinelli made his feature film debut in Rebecca Miller's Angela in 1995 and came to the attention of critics in the TV-movie The Price of Love later that year. In 1996, Facinelli played opposite future wife Jennie Garth in An Unfinished Affair. Other TV roles followed, including a part in After Jimmy (1996) and a college dropout in Calm at Sunset. Facinelli co-starred with Amanda Peet and Michael Vartan in the 1997 AIDS-themed drama Touch Me (1997) and co-starred as a high school student in two 1998 features with Ethan Embry and Breckin Meyer, Dancer, Texas Pop. 81, and Can't Hardly Wait, which starred Jennifer Love Hewitt and co-starred Melissa Joan Hart and Jerry O'Connell.
Facinelli appeared in the sci-fi film Supernova starring James Spader in 2000. He made appearances in Riding in Cars with Boys in 2001 and Scorpion King in 2002, followed by a leading role in the Fox drama Fastlane. Facinelli had a recurring role in the HBO series Six Feet Under in 2004 and a role in the FX original series Damages beginning in 2007. Facinelli starred inHollow Man 2 with Christian Slater. It was released direct-to-video in May 2006.
After wrapping up Finding Amanda with Matthew Broderick, Facinelli played Carlisle Cullen in the film adaptation of Twilight, based on the book by Stephenie Meyer. Facinelli reprised his role in 2009's sequel to Twilight, The Twilight Saga: New Moon, and will appear in 2010's The Twilight Saga: Eclipse.
He costars as Dr. Fitch Cooper in the Showtime dark comedy series Nurse Jackie.
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