From the mid- to late '60s, Coffey was a Detroit session fixture, appearing on such mainstream hits and cult classics as Darrell Banks' monumental "Open the Door to Your Heart," Carl Carlton's "Competition Ain't Nothing," and Tobi Lark's "Happiness Is Here." His inventive playing is the tissue that connects an untold number of crowd favorites within Britain's Northern soul club culture. Around 1968 Coffey also began working steadily at Motown, beginning with the Temptations' gritty "I Wish It Would Rain." He went on to appear on the group's landmark efforts "Cloud Nine" and "Ball of Confusion," pushing the Motown sound into increasingly funky territory with his ingenious use of a wah-wah pedal, one of several technological innovations he introduced to tweak The Sound of Young America. Beginning with Jack Montgomery's Scepter release "Dearly Beloved," Coffey concurrently added arranging and producing to his slate, teaming with local session drummer Mike Theodore to found their own production firm, Theo-Coff. The duo quickly hit paydirt helming a demo tape for the blue-eyed psych-soul combo the Sunliners, landing a production deal with MGM's Maverick subsidiary. Six months later, Maverick also signed Coffey to a solo contract, releasing his psych-funk classic Hair & Thangs and scoring a Midwestern smash in 1969 with his fuzz-laden instrumental reading of the Isley Brothers' "It's Your Thing."

MGM shut down Maverick in late 1969. While the Sunliners renamed themselves Rare Earth, signing to Motown for a series of hits, Coffey resumed his session career, appearing on classics including Edwin Starr's "War" and Freda Payne's "Band of Gold." In 1971 he landed with former Maverick head Clarence Avant's new Sussex label as an artist and as a staff producer, scoring a Top Ten hit with the single "Scorpio," a now-classic funk effort renowned for its much-sampled drum breaks. Its follow-up, "Taurus," was also a commercial success, while LPs including Evolution and Goin' for Myself generated familiar samples for acts spanning from Public Enemy to the Beastie Boys to LL Cool J. As a producer, Coffey is probably best remembered for Gallery's 1972 soft rock smash "Nice to Be with You." In collaboration with Theodore, he also helmed a series of disco hits after jumping to the Westbound label in 1974, most notably CJ & Co's "We Got Our Own Thing" and the Tempest Trio's "Love Machine." For Westbound Coffey scored the 1974 blaxploitation film Black Belt Jones, although his solo records from the label have aged poorly in comparison to his Sussex efforts.

After the label dissolved in 1980, he again returned to session work before resurfacing in 1989 with the lite-jazz outing Under the Moonlight. In 2004 Coffey published the memoir Guitars, Bars and Motown Superstars. The first decade of the 21st century showed a renewed interest in Coffey's solo work as three different compilations were released: Vampi Soul's Big City Funk: Original Old School Breaks & Heavy Guitar Soul; Live Wire: The Westbound Years 1975-1978; and Fuel's excellent Absolutely the Best of Dennis Coffey. He was honored by the Detroit Music Awards in 2011 with a Distinguished Achievement Award. (Coffey was also nominated in the video category for the unlikely success of his YouTube entry, an instrumental version of Cee Lo's "Fuck You.") In April of that year, at the age of 70, Coffey also released a scorching self-titled album of all new material for Strut with vocal contributions from Mayer Hawthorne, the Detroit Cobras' Rachel Nagy, Paolo Nutini, Lisa Kekaula of the BellRays, Fanny Franklin of Orgone, Kings Go Forth, and backing by a slew of Detroit musicians.