While working a series of odd jobs, including a tenure as a foot messenger for Esquire magazine, Richman attempted to find a venue to perform his music, but his simple songs and adenoidal voice were roundly rejected; he ultimately moved back to Boston in 1970, where he formed the first incarnation of the influential proto-punk band the Modern Lovers with guitarist John Felice, drummer David Robinson and bassist Rolfe Anderson. Within a few months, Anderson had been replaced by Ernie Brooks, and keyboardist Jerry Harrison stepped in for Felice. After recording some demos with Kim Fowley in the spring of 1971 (unissued until 1981), in 1973, the Modern Lovers (with producer John Cale) recorded the demos which comprised their seminal self-titled debut, featuring long-standing Richman favorites like "Roadrunner," "Pablo Picasso" and "Hospital." Problems with their label, however, blocked the songs' release until 1976; at the same time, Richman wanted to quiet the group's minimalist, garagey sound, leading to their breakup in 1973.

Eventually, Richman formed a new, acoustic Modern Lovers with guitarist Leroy Radcliffe, Rubinoos bassist Greg "Curly" Keranen and drummer Robinson. In 1977, they debuted with Jonathan Richman & the Modern Lovers, which emphasized the doo-wop flavor and wry pop melodies that remained hallmarks of Richman's career. That same year, the group issued Rock 'N' Roll With the Modern Lovers (with D. Sharpe on drums) and scored a major European hit with the instrumental "Egyptian Reggae." A year later, Richman went solo, and in 1979 issued Back in Your Life.

After a period of self-imposed exile, he resurfaced in 1983 with Jonathan Sings A series of strong pop records followed, including 1985's Rockin' & Romance, 1986's It's Time for Jonathan Richman & the Modern Lovers (recorded with Andy Paley), and Modern Lovers 88. In 1990, he released the self-explanatory Jonathan Goes Country; later, he made another left turn with 1993's Jonathan, Te Vas a Emocionar!, a collection of Latin-influenced songs performed entirely in Spanish. No matter what path his music took, however, Richman's cult following remained fiercely loyal, and saw its ranks expand courtesy of his frequent appearances on the NBC program Late Night With Conan O'Brien; in 1998, he was also prominently featured in the hit film comedy There's Something About Mary. I'm So Confused appeared later that year. Richman began dipping his toes into slightly more sophisticated musical forms with 2001's Her Mystery Not of High Heels and Eye Shadow, which also documented his continuing interest in the Spanish language, as did 2004's Not So Much to Be Loved as to Love.