Hampton began his career following in the footsteps of brother and fellow comic book creator Bo Hampton. Both Scott and Bo studied under Will Eisner in 1976. Scott's first professional comics work was the three-page story "Victims" published in Warren Publishing's Vampirella #101 in 1981. Scott's work on Silverheels from Pacific Comics in 1983 is regarded as the first continuing painted comic (of U.S. origin).
Working as a freelance comic book artist, Hampton has illustrated such iconic properties as Batman, Sandman, Black Widow, Hellraiser, and Star Trek in addition to work on his creator-owned projects such as The Upturned Stone.
His works include Spookhouse, released in 2004 by IDW Publishing, in which he adapted his favorite ghost stories into sequential form, and Batman: Gotham County Line from DC Comics in 2005. Hampton is currently working full-time on the creator-owned series Simon Dark with writer Steve Niles for DC Comics.
Hampton has illustrated cards for the Magic: The Gathering collectible card game.