Litt produced the R.E.M. albums Document (1987), Green (1988), Out of Time (1991), Automatic for the People (1992), Monster (1994) and New Adventures in Hi-Fi (1996). In 1997, R.E.M. and Litt discontinued their collaboration and the band had Patrick McCarthy produce their subsequent albums
Apart from R.E.M., the most commercially successful act Litt worked with was Nirvana, for whom he mixed the singles "Heart-Shaped Box" and "All Apologies" from the 1993 album In Utero, and the posthumous release MTV Unplugged in New York (1994). Litt also remixed "Pennyroyal Tea," and the remix was set to be released on the single, but the single was retracted shortly after Kurt Cobain's death. His remix can be found on Nirvana, Nirvana's greatest hits collection. In 1999 and the 2000s, Litt worked with Incubus to produce two of their records Make Yourself (1999) and Morning View (2001). Litt also mixed songs for Hole including "Miss World", "Asking For It", "Jennifer's Body", and "Softer, Softest" off their CD "Live Through This".
Scott Litt has appeared in episode 6 of the BBC series Seven Ages of Rock, "left of the dial".