Two years later, Wynn formed the trio 15 Minutes with two members of Alternate Learning, bass player Carolyn O'Rourke and drummer Eric Landers. With 15 Minutes, Wynn wrote and produced the 1981 single "That's What You Always Say," b/w "Last Chance For You," which he engineered with Alternate Learning's frontman, Scott Miller. The A-side, "That's What You Always Say," was later performed by the Dream Syndicate.
The Dream Syndicate's eponymous EP was released on Wynn's own label, Down There (which folded by the end of the band's career). Though they were popular with critics, an influence on other musicians, and signed briefly to a major label, the Dream Syndicate were not commercially successful. They did establish, however, the fan base on which Wynn built his solo career. Dream Syndicate reunited in 2013 for a series of gigs in Europe and USA.
Wynn broke up The Dream Syndicate in 1989 to redefine (or "undefine") himself, and has since released a number of solo albums exploring various musical styles. His first solo album, Kerosene Man (on which Dream Syndicate bassist Mark Walton played also) included a duet with Johnette Napolitano of Concrete Blonde, backing work by bassist Fernando Saunders, drummer D. J. Bonebrake from the L.A. punk band X, Howe Gelb of Giant Sand and saxophonist Steve Berlin from Los Lobos. Peter Buck, from R.E.M., played on its follow-up, Dazzling Display, and co-wrote the title song. After 1994's Fluorescent, he left Los Angeles for New York. Backing on Melting in the Dark (1996) was provided by the Boston band Come.
Here Come the Miracles (2001) was his best-selling solo album to date, and the best-reviewed, appearing at year's end on numerous critical Top Ten lists.
In 1993, Wynn worked with singer-songwriter Sam Lapides producing Dream Syndicate song "Burn" for Lapides' band Ghosthouse. They later recorded a live version of the song. He wrote the song "Black Magic" for Ghosthouse's album "Thing Called Life". Then in 2001 he worked with Lapides again, providing vocals and guitar work on another Dream Syndicate song "Merittville" which was released by Inbetweens Records.
The double CD From a Man of Mysteries: A Steve Wynn Tribute was released by the German label Blue Rose in 2004 and features Wynn's songs performed by the likes of Concrete Blonde, the Silos, Chuck Prophet, The Minus 5, Russ Tolman of True West and others.