David also studied psychology at Boston University, receiving a BA. He served in the U.S. Army in West Germany. In the mid-1950s, he worked as a Hollywood production assistant on the Marilyn Monroe films Bus Stop and The Prince and the Showgirl. David later stated that he grew "disenchanted with conventional filming. The glamour had faded and the filming of take after take had become tedious." By 1957 he had teamed up with Albert to shoot two documentaries behind the Iron Curtain, Russian Close-Up (credited to Albert Maysles alone) and Youth in Poland, the latter of which was broadcast on NBC.

Albert originally pursued a career as a psychology professor and researcher. After serving in World War II, Albert obtained a BA from Syracuse University and MA in psychology from Boston University. He taught psychology at Boston University for three years, also working as a research assistant at a mental hospital and as head of a research project at Massachusetts General Hospital. As an outgrowth of his research work, he traveled to Russia to photograph a mental hospital, and returned the following year with a camera provided by CBS to film his first documentary, Psychiatry in Russia (1955). Although CBS did not air the film, it was televised on NBC, on the public broadcasting station WGBH-TV in Boston, and on Canadian network television.

The Maysles brothers made over 30 films together. They are best known for three documentaries made in the late 1960s and early 1970s: Salesman (1969), Gimme Shelter (1970), and Grey Gardens (1975). Salesman documents the work of a group of door-to-door Bible salesmen in New England and Florida. Gimme Shelter, a film about The Rolling Stones' 1969 U.S. tour culminating in the disastrous Altamont Free Concert, unexpectedly captured on film the altercation between Altamont attendee Meredith Hunter and Hells Angel Alan Passaro that resulted in Hunter's death. Film footage shows Hunter drawing and pointing a revolver just before being stabbed by Passaro, who was later acquitted of Hunter's murder on self-defense grounds after the jury viewed the footage. Grey Gardens depicts the lives of a reclusive upper-class mother and daughter, "Big Edie" and "Little Edie" Beale (who were, respectively, the aunt and cousin of Jacqueline Kennedy Onassis), residing in a derelict mansion in East Hampton, New York. In order to Finance these films and others, the Maysles also made commercials for clients such as IBM, Shell Oil, and Merrill Lynch.

Many of the Maysles' documentaries focus on art, artists and Musicians. The Maysles documented The Beatles' first visit to the United States in 1964, and a 1965 conceptual art project by Yoko Ono called "Cut Piece" in which she sat on the stage of Carnegie Hall while audience members cut off her clothing with scissors. Several Maysles films document art projects by Christo and Jeanne-Claude over a three-decade period, from 1974 when Christo's Valley Curtain was nominated for an Academy Award, to 2005 when The Gates (started in 1979 and completed by Albert after David's death) headlined New York's Tribeca Film Festival. Other Maysles subjects include Marlon Brando, Truman Capote, Vladimir Horowitz, and Seiji Ozawa.

David Maysles, the younger brother, died of a stroke on January 3, 1987, seven days shy of his 56th birthday, in New York City. Following his death, Albert was involved in litigation with David's widow over the terms of a financial settlement. According to David's daughter Celia Maysles, this resulted in the family developing a "code of silence" regarding David. In 2007, Celia released a documentary about her father, Wild Blue Yonder, which included interviews with Albert.

The Maysles' films are considered examples of the style known as direct cinema. The brothers would let the story unfold as the camera rolled, rather than planning what exactly they wanted to shoot, in keeping with Albert Maysles' stated approach, "Remember, as a documentarian you are an observer, an author but not a Director, a discoverer, not a controller." However, the brothers also received criticism from those who thought that they had actually planned or otherwise influenced scenes. Most notably, Pauline Kael's negative review of the film Gimme Shelter in The New Yorker included a harsh accusation that much of Gimme Shelter and Salesman had been staged and that the main subject of Salesman, Paul Brennan, was not a Bible salesman as the film portrayed, but was actually a roofing-and-siding salesman recruited as a professional actor. The Maysles brothers threatened legal action against The New Yorker after this accusation. They also sent an open letter to The New Yorker refuting Kael's claims; however, because the magazine at the time did not publish letters, the letter did not appear in print until 1996. In the case of Grey Gardens, the brothers were also accused of unfairly exploiting their subjects.

After his brother's death, Albert Maysles continued to make films. His notable works include LaLee's Kin: The Legacy of Cotton (2001, co-directed with Deborah Dickson and Susan Froemke), which focused on the struggles of a poor African-American family living in the contemporary Mississippi Delta, and was nominated for an Academy Award for Best Documentary Feature; and The Love We Make (2011, co-directed with Bradley Kaplan) which documented Paul McCartney's experiences in New York City following the September 11, 2001 attacks, and premiered on Showtime on September 10, 2011, the eve of the tenth anniversary of the attacks.

The Maysles brothers' films Salesman and Grey Gardens have been preserved in the Library of Congress' National Film Registry as being culturally, historically or aesthetically significant. In May 2002, Ralph Blumenthal in The New York Times referred to Albert as "the dean of documentary film making" and Jean-Luc Godard once called Albert "the best American cameraman". The moving image collection of Albert and David Maysles is held at the Academy Film Archive.

An HBO film entitled Grey Gardens was released in 2009 that dramatized the story of the Beales and the Maysles brothers' making of the original documentary, with actors portraying the Beales, the Maysles, and other involved parties. The film featured Arye Gross as Albert and Justin Louis as David.

Albert continued the series of documentaries begun with David about the public art of Christo and Jeanne-Claude. He also contributed cinematography to Leon Gast's Academy Award-winning documentary When We Were Kings, about the "Rumble in the Jungle" Muhammad Ali – George Foreman heavyweight championship boxing match. In 2005, Albert founded the Maysles Documentary Center, a nonprofit organization dedicated to the exhibition and production of documentary films that inspire dialogue and action, located in Harlem.

In 1999 Eastman Kodak saluted Albert Maysles as one of the world's 100 finest cinematographers. In 2001, Albert received the Sundance Film Festival 2001 Cinematography Award for Documentaries for LaLee's Kin: The Legacy of Cotton as well as the DuPont Columbia Gold Baton Award. In 2005, he was given a lifetime achievement award at the Czech film festival AFO (Academia Film Olomouc) and in 2011 a lifetime achievement award from Sheffield Doc/Fest. He was awarded a 2013 National Medal of Arts by President Barack Obama on July 28, 2014.

In 2015 the cable network, IFC released a mockumentary series titled, "Documentary Now!" . IFC is owned and operated by AMC Networks Inc., and available across multiple platforms. The series pilot episode is titled "Sandy Passage" and follows two women named "Big Vivvy" and "Little Vivvy" and takes "An in depth look at the daily lives of two aging socialites and their crumbling estate." It was inspired and pays homage to Grey Gardens in a comedic way.