Jackson is known for his role as the voice of Ghostface in the Scream slasher films. He has also appeared in animated films and television programs such as Disney's The Book of Pooh as well as Nickelodeon's The Wild Thornberry Movie. He also does the voice of the maniacal monkey genius Mojo JoJo, The Rowdyruff Boy, and Butch on The Powerpuff Girls.
Jackson has also played an active role in the electronic games industry; voicing monsters for Dungeons and Dragons; heroes for Galleon and Baldur's Gate. He has worked for several Star Wars video games as the commander of Triton Squad for a example and Star Trek programs. On top of that, he provides voices for all the original cats on the Catz virtual pet program; he also contributed to Final Fantasy X and King's Quest VII and has done educational programs for The Learning Company and Broderbund. For American McGee's Alice, Jackson provided the voice for the Chesire Cat and Jabberwock. For an Electronic Arts Sherlock Homes game, Jackson did over thirty characters. Jackson played the tyrant Colonel Nohman from Zone of the Enders, and Zone of the Enders: The 2nd Runner. He also did the voice of John O'Conner in Delphine Software International's Fade to Black.