Pearlstein was born in Pittsburgh, Pennsylvania. He studied at the Carnegie Institute of Technology and received his Masters in art history at New York University. He was a friend of Andy Warhol from college and he accompanied Warhol to Manhattan from Pittsburgh in 1949. Warhol and Pearlstein subleased an eighth-floor walkup tenement apartment on St. Mark's Place (and Avenue A) for the summer. According to Pearlstein, "The bathtub was in the kitchen and it was usually full of roaches, incredible roaches." When they moved a few months later to the large front room of dancer Francesca Boas's loft on West 23rd Street, Warhol sent out address change cards in small envelopes filled with glitter announcing: "I've moved from one roach-ridden apartment to another."
During the 1950s Pearlstein exhibited abstract expressionist landscape paintings. Around 1958 he began to attend weekly figure drawing drawing sessions at the studio of Mercedes Matter. In 1961 Pearlstein began to make paintings of nude couples based upon his drawings, and in 1962 he began painting directly from the model in a less painterly and more realistic style. In so doing, he demonstrated that figurative realism could once again be made into a vital art form. In an article published in Arts Magazine in April, 1963, Sidney Tillim wrote that "[Pearlstein] has not only regained the figure for painting; he has put it behind the plane and in deep space without recourse to nostalgia (history) or fashion (new images of man) ... He paints the nude not as a symbol of beauty and pure form but as a human factâ€”implicitly imperfect".
Pearlstein's early landscape paintingsâ€”usually rock-strewn hillsides in which every angle, shadow, and shape was seen with a clinical clarityâ€”foreshadow his treatment of the nude as a natural phenomenon devoid of any identity other than the attributes of sex and skin color. Before modernism, painting and sculpture presented the human body in every conceivable pose and situation sanctioned by history, religion, or mythology, but the twentieth century brought a new method of comprehending what we see as form for its own sake. In Pearlstein's paintings, the human body, placed in a corner of a floodlighted studio, assumes a new range of plastic realities, as the mass and weight of the body are emphasized in the unstudied character of the pose. The point of view frequently results in radical cropping of the figure at the edge of the canvas. The painting Models With Mirror is an example of Pearlstein's concern for the body as form.
Pearlstein's work is in 63 museums collections in the United States, including the Art Institute of Chicago, The Cleveland Museum of Art, the Corcoran Gallery of Art, Hirshhorn Museum and Sculpture Garden, Kemper Museum of Contemporary Art, Metropolitan Museum of Art, The Museum of Modern Art and Whitney Museum of American Art amongst others. The Milwaukee Art Museum honored him with a retrospective exhibition in 1983 and accompanied the exhibition with a monograph on his complete paintings. He recently showed at the Century Association, New York; Frye Art Museum, Seattle; Galerie Haas, Zurich; and Galerie Haas & Fuchs, Berlin, Germany.
Since the mid-1950s Pearlstein has received several awards, most recently, the National Council of Arts Administrators Visual Artist Award; The Benjamin West Clinedinst Memorial Medal, The Artists Fellowship, Inc., New York, NY; and honorary doctorate degrees from Brooklyn College, NY, Center for Creative Studies and the College of Art & Design, Detroit, MI, and New York Academy of Arts, New York, NY. Pearlstein is a former President of the American Academy of Arts and Letters.