Zane was born in Chicago, Illinois to William George Zane, Sr. and Thalia, who ran a medical technical school. His father was American and his mother was born in Greece. He has an older sister, Lisa Zane, who is also an actress. Zane graduated from the Francis W. Parker School, where two of his classmates were Daryl Hannah and Jennifer Beals.
Zane's first prominent screen role was in Back to the Future (1985) playing Biff Tannen's friend Match. He landed the role as a fluke by appearing nonchalant, dressed in a T-shirt. Zane later reprised the role for the 1989 sequel, Back to the Future II. Zane is perhaps best known for playing Caledon Hockley in the 1997 movie blockbuster Titanic and the eponymous classic comic book hero in The Phantom. His most recent role is in the controversial Turkish film Valley of the Wolves Iraq Zane portrays Special Forces commander Sam William Marshall, a violent, greedy American soldier who massacres innocent Iraqis.
Zane keeps busy in other parts of the entertainment industry as well. He is a singer and can occasionally be seen in various Broadway shows. He also played the voice of Xehanort (then known as Ansem) in Squaresoft and Disney's renowned video game Kingdom Hearts, but was replaced by Richard Epcar for Kingdom Hearts II. Zane also had a recurring role in the popular television series Charmed in which he played poetry loving ex-demon Drake.
Premature hair loss has not diminished Zane's acting career. Sometimes, while in character, he wears a wig, although he usually shaves his head while not in character and has been forefront in promoting this look. Zane is also an avid swimmer, therefore shaving his head aids his hydrodynamics while moving through the water.
In 1999, Zane participated in the first Gumball 3000 rally, driving a 1964 Aston Martin DB5. He was featured in the music video, Epiphany, by Staind.
Zane married co-actress Lisa Collins in 1989. The couple divorced in 1995. He was also engaged for a time to Chilean actress Leonor Varela, his costar in the 1999 television movie Cleopatra. As of 2006, Zane is engaged to marry British actress Kelly Brook.