David Armstrong was born in 1954, in Arlington, Massachusetts, and graduated from the Satya Community School, an alternative high school in Cambridge, Massachusetts, where he met Nan Goldin at the age of 14. He then enrolled at the School of the Museum of Fine Arts in Boston as a painting major, but soon switched his concentration to photography after studying alongside Goldin, with whom he shared an apartment. He attended the School of the Museum of Fine Arts and Cooper Union from 1974–78, and earned a BFA from Tufts University in 1988.

During the late 1970s, Armstrong became associated with the “Boston School” of photography, which included artists such as Nan Goldin, Mark Morrisroe, and Jack Pierson. Armstrong first received critical attention for his intimate portraits of men. In the 1990s, he began photographing cityscapes and landscapes in soft focus to contrast with the sharpness of his portraits.

In 1981, Armstrong created a series of black-and-white portraits which he showed at PS1’s “New York/New Wave” exhibition. In 1996, Elisabeth Sussman, curator of photographs at the Whitney Museum, enlisted Armstrong’s help in composing Nan Goldin’s first retrospective. She gained such respect for Armstrong’s eye, she acquired work for the Whitney Museum’s permanent collection, and he was subsequently featured in the 1994 Whitney Biennial.