Woods' career has been noted for the intense characters he has chosen, the earliest of which was his portrayal of a sadistic murderer in 1979's The Onion Field. He was nominated for an Academy Award twice: the first in 1987 for Best Actor in Salvador and again in 1996 for Best Supporting Actor for his acclaimed performance as Byron De La Beckwith in Ghosts of Mississippi. He has also garnered critical praise for his voice work for Hades in Disney's Hercules. His personal favorite of all of his roles, however, is as the domineering gangster Max in Sergio Leone's gangster epic Once Upon A Time In America (1984).

He was briefly considered for the role of The Joker by Tim Burton and Sam Hamm for the Batman film in 1989. Hamm recalls that he and Burton thought, "James Woods would be good and wouldn't need any makeup, which would save a couple of hours' work every morning." The role ended up going to Jack Nicholson. Quentin Tarantino wrote a part in Reservoir Dogs with Woods in mind, but his agent rejected the script without showing it to the actor. When Woods learned of this some time later, he fired the agent. Woods was also considered for the part of Donald Kimball in American Psycho, but he turned it down. The part was given to Willem Dafoe.

Woods appeared as himself in the episode of The Simpsons entitled "Homer and Apu" and in an episode of Family Guy entitled "Peter's Got Woods". In 2006, Woods starred opposite Cuba Gooding Jr. in the political thriller End Game. Also in 2006, Woods played himself in the premiere episode of Entourage's third season. He also starred in Grand Theft Auto: San Andreas as Mike Toreno and voiced the falcon in Stuart Little 2.

Woods stars in the new CBS legal drama Shark. Woods plays an infamous Los Angeles defense lawyer who, growing disillusioned, becomes a prosecutor. (wikipedia.org)