Born and raised in Massachusetts, this son of Russian Jewish immigrants developed a childhood interest in photography. After receiving his MA in psychology, Maysles traveled to Russia and shot photographs inside mental hospitals. Although he was unsuccessful in selling those pictures, he did manage to obtain a movie camera from CBS the following year and on a return visit shot his first documentary "Psychiatry in Russia" (1955). While no network would touch the finished product, he did find an outlet at Boston's public television station WGBH which aired the documentary. He and his brother David shot footage of a student revolt in Poland which aired on NBC in 1957. Shortly thereafter, the brothers met Pennebaker who in turn introduced them to Drew and Leacock.

After "Primary", the Maysles were selected by Grenada Television to shoot the US arrival of a new rock'n'roll band, resulting in "What's Happening! The Beatles in the USA" (1964). Although there was interest in studio distribution, the band's contract to make "A Hard Day's Night" precluded any widespread showings. CBS purchased a shortened version and aired it with narration provided by Carol Burnett. Often collaborating with Charlotte Zwerin, the Maysles brothers produced one of their best-known works in 1968. "Salesman", a look at door-to-door bible sellers in Boston, which for various reasons also did not gain widespread exposure until a 1994 airing on PBS. "Gimme Shelter" (1970), on the other hand, garnered much controversy. This record of a Rolling Stones concert stirred much debate over its capturing of the knifing death of one of the concertgoers. The moral issues raised by the filmmaker's "detached observer" status were hotly debated. A similar fate befell "Grey Gardens" (1976), their portrait of the Beales, a mother-daughter living in seclusion in a rundown East Hampton mansion. A pathetic but human look at two women who share their living space with a multitude of felines, the film is a fascinating depiction of co-dependence and resentment with particular emphasis on the mother-daughter dynamic. At the time of its release, "Grey Gardens" divided critics, some of whom praised it as one of the year's best films while others found it tasteless and exploitative.

The brothers received their sole Oscar nomination in 1973 for the first of several collaborations with the artist Christo. "Christo's Valley Curtain" (1973) explored the artist's hanging a nine-ton orange nylon fabric in Rifle Gap, Colorado which was destroyed by nature after a day. Without explaining the why of Christo, the film documents the project. Similarly, the others in the series "Running Fence" (1978), "Islands" (1986), "Christo in Paris" (1990) and "Umbrellas" (1995) all merely show the artist at work.

In the 1980s, Maysles turned his attentions to profiling classical musicians like Seiji Ozawa and Vladimir Horowitz. After David's death in 1987, he partnered with Susan Froemke and embarked on a series of made-for-cable documentaries, including "Abortion: Desperate Choices" (HBO, 1992) and "Letting Go: A Hospice Journey" (HBO, 1996). More recently, he chronicled the development of the Los Angeles Center in "Concert of Wills: Making the Getty Center" (1997).