He spent six years in the league with four teams, including the Green Bay Packers, the Chicago Bears and the Washington Redskins, though his playing time and on-field success in the NFL was limited.

Wuerffel also played one season in NFL Europe, where he led the Rhein Fire to a league championship in World Bowl 2000.

After retiring from professional football, Wuerffel returned to New Orleans to work with Desire Street Ministries, a nonprofit organization that seeks to help impoverished neighborhoods through spiritual and community development.

[1] Under Wuerffel, Desire Street Ministries moved its headquarters to Atlanta and expanded its programs to other inner cities in the American South.

[6] One of the most decorated players in Florida's football history,[6] he was a key member of the Gators teams that won four consecutive Southeastern Conference titles between 1993 and 1996.

Wuerffel won the 1996 Heisman Trophy,[20] as the outstanding college football player in America, while quarterbacking the Gators into their second consecutive Bowl Alliance national championship game with help from teammates Fred Taylor at running back; Reidel Anthony, Ike Hilliard, and Jacquez Green at wide receiver; and Jeff Mitchell on the offensive line.

Wuerffel and the Gators won the 1996 national championship in decisive fashion by defeating the Florida State Seminoles 52–20 in the Sugar Bowl.

[22] Wuerffel declined to be included on Playboy magazine's All-America team as well as its Scholar-Athlete of the Year award, saying, "That's not the type of person I am or would like to portray myself as.

[27] He was selected to potentially serve as the number three quarterback, as the team already had Heath Shuler and Jim Everett on the roster under new head coach Mike Ditka.

[32] Wuerffel began work at Desire Street Ministries, a nonprofit, faith-based organization focusing on spiritual and community development in areas of New Orleans.

[33][34] It is awarded annually by the All Sports Association of Fort Walton Beach, Florida to the athlete who best exemplifies Wuerffel's character on the field of play and in the classroom.

[33][34] In June 2011, The Gainesville Sun reported that Wuerffel was suffering from Guillain–Barré syndrome, a disorder of the nervous system, and was undergoing treatment for it.

[36] A small stretch of road between the Mid-Bay Bridge and Highway 98 in Destin, still his parents' home,[36] has been dedicated as "Danny Wuerffel Way" by the Florida state legislature.