Mapplethorpe was born in Floral Park, Queens, New York City, the son of Joan Dorothy (Maxey) and Harry Irving Mapplethorpe, an electrical engineer. He was of English, Irish, and German descent, and grew up as a Roman Catholic in Our Lady of the Snows Parish. He had three brothers and two sisters. He studied for a Bachelor of Fine Arts from the Pratt Institute in Brooklyn, where he majored in Graphic Arts, though he dropped out in 1969 before finishing his degree. Mapplethorpe lived with his close friend Patti Smith from 1967 to 1972, and she supported him by working in bookstores. They created art together, and maintained a close relationship.
Mapplethorpe took his first photographs in the late 1960s or early 1970s using a Polaroid camera. In 1972 he met art curator Sam Wagstaff who would become his mentor and lifetime companion. In the mid-1970s Wagstaff acquired a Hasselblad medium-format camera and Mapplethorpe began taking photographs of a wide circle of friends and acquaintances, including artists, composers, and socialites. During this time, he became friends with New Orleans artist George Dureau, whose work had such a profound impact on Mapplethorpe that he restaged many of Dureau's early photographs. From 1977 until 1980, Mapplethorpe was the lover of writer and Drummer magazine editor Jack Fritscher, who introduced him to Mineshaft.
By the 1980s Mapplethorpe's subject matter focused on statuesque male and female nudes, delicate flower still lifes, and highly formal portraits of artists and celebrities. Mapplethorpe's first studio was at 24 Bond Street in Manhattan. In the 1980s, Wagstaff bought a top-floor loft at 35 West 23rd Street for Robert, where he resided, also using it as a photo-shoot studio. He kept the Bond Street loft as his darkroom. In 1988, Mapplethorpe selected Patricia Morrisroe to write his biography, which was based on more than 300 interviews with celebrities, critics, lovers, and Mapplethorpe himself.
Mapplethorpe died on the morning of March 9, 1989 at the age of 42 due to complications from HIV/AIDS, in a Boston, Massachusetts hospital. His body was cremated. His ashes are interred at St. John's Cemetery, Queens in New York, at his mother's grave-site, etched "Maxey".
Nearly a year before his death, the ailing Mapplethorpe helped found the Robert Mapplethorpe Foundation, Inc. His vision for the Foundation was that it would be "the appropriate vehicle to protect his work, to advance his creative vision, and to promote the causes he cared about". Since his death, the Foundation has not only functioned as his official estate and helped promote his work throughout the world, but has also raised and donated millions of dollars to fund medical research in the fight against AIDS and HIV infection and to promote fine art photography at the institutional level. The Foundation also determines which galleries represent Mapplethorpe's art. In 2011, the Robert Mapplethorpe Foundation donated the Robert Mapplethorpe Archive, spanning from 1970 to 1989, to the Getty Research Institute.