Ryder was born on February 26, 1945, in Hamtramck, Michigan. He spent his high school years in Warren, Michigan, a suburb north of Detroit. He formed his first band, Tempest, when he was in high school, and the group gained some notice playing at a Detroit soul music club called The Village.[4] Ryder next appeared fronting a band named Billy Lee & The Rivieras, which had limited success until they met songwriter / record producer Bob Crewe. He selected his stage name when he saw "Mitch Ryder" in the Manhattan telephone directory and renamed the group Mitch Ryder & The Detroit Wheels. They recorded several hit records for his DynoVoice Records and New Voice labels in the mid to late 1960s, most notably 1964's "Devil with a Blue Dress On", their highest-charting single at number four, as well as "Jenny Take a Ride!", which reached number 10 in 1965, and "Sock It to Me, Baby!", a number six hit in 1967. The Detroit Wheels were John Badanjek on drums, Mark Manko on lead guitar, Joe Kubert (not to be confused with the comic book illustrator Joe Kubert) on rhythm guitar, Jim McCarty (not to be confused with the Yardbirds drummer of the same name) on lead guitar and Jim McAllister on bass.

Mitch Ryder and the Detroit Wheels performing in 1966

In December 1966, producer Bob Crewe's vision for Mitch as a blue-eyed soul singer backed by a horn band (a la Wilson Pickett, Joe Tex, etc.) was put into motion. They assembled a 10 piece band of white R&B musicians: from Baltimore, Maryland; Jimmy Wilson (trumpet), Bob Shipley (sax), Jimmy Loomis (sax), Don Lehnhoff (trombone), Frank Invernizzi (organ); from Chicago, Illinois; John Siomos (drums), Bob Slawson (guitar), Carmine Riale (bass guitar); from Miami, Florida; Andy Dio (trumpet); from New York; Johnny ? (lead guitar). The band rehearsed for a month in a dance studio above the Cheetah, a night club at Broadway and 53rd, then hit the road as The Mitch Ryder Show in February 1967.

Ryder was the last person to perform with Otis Redding; they performed the song "Knock On Wood", on December 9, 1967, in Cleveland, Ohio, on a local TV show called Upbeat. Redding and four members of his touring band, The Bar-Kays, died in a plane crash near Madison, Wisconsin the following day, December 10, 1967.

Ryder's musical endeavors were less successful after the early 1970s. Ryder's participation with the Detroit Wheels ended just as the counterculture was becoming dominant in 1968. During 1968, trumpeters Mike Thuroff and John Stefan were hired to tour with his horn section and band. Thuroff and Stefan also recorded the trumpet parts of Ryder's song, "Ring My Bell". This song was not permitted to be played by radio in many states due to its sexual innuendos. Ryder had one hit single from that period, a cover version of "What Now, My Love". His last successful ensemble band was Detroit. The only original Wheel in the group was the drummer John Badanjek; other members were guitarists Steve Hunter, Robert Gillespie, and Brett Tuggle, organist Harry Phillips, and bassist W.R. Cooke. A single album was released by this grouping, a 1971 self-titled LP issued on Paramount Records (US #176 in 1972). They had a hit with their version of the Lou Reed-penned song "Rock & Roll", which Reed liked enough to ask Steve Hunter to join his backing band.

According to AllMusic (which calls Ryder "the unsung hero" of Michigan rock and roll), Ryder withdrew from music in 1973 after experiencing throat trouble, moving to Colorado with his wife and taking up writing and painting. In 1983, Ryder returned to a major label with the John Mellencamp-produced album Never Kick a Sleeping Dog. The album featured a cover version of the Prince song "When You Were Mine", which was Ryder's last score on the Billboard Hot 100.

Ryder continues to record and tour in the United States and Europe. In 2005, Mitch Ryder & The Detroit Wheels were inducted into the Michigan Rock and Roll Legends Hall of Fame. In 2009, Mitch Ryder was inducted as a solo artist. On February 14, 2012, Ryder released The Promise, his first US release in almost 30 years.