Reinhardt was born in Buffalo, New York, and lived with his family in the Riverside section along the Niagara River. His cousin Otto and he were close, as well as the extended family, but work took his father to New York City. He later studied art history at Columbia College of Columbia University, where he was a close friend of Robert Lax and Thomas Merton. The three developed similar concepts of simplicity in different directions. Reinhardt considered himself a Painter from a very early age and began winning prizes for painting in grade school and high school. Feeling that he had already acquired all the technical skills in high school he turned down scholarships at art schools and accepted a full scholarship at Columbia University which he attended from 1931 to 1935. He took painting classes as an undergraduate at Columbia's Teachers College and after graduation began to study painting with Carl Holty and Francis Criss at the American Artists School, while simultaneously studying portraiture at the National Academy of Design under Karl Anderson.

Upon finishing college he was accredited as a Painter by Burgoyne Diller, which allowed him to work from 1936 until 1940 for the WPA Federal Art Project, easel division. Sponsored by Holty he became a member of the American Abstract Artists group, with whom he exhibited for the next decade. Reinhardt described his association with the group as "one of the greatest things that ever happened to me". He participated in group exhibitions at the Peggy Guggenheim Gallery, and he had his first one-man show at the Artists Gallery in 1943. He then went on to be represented by Betty Parsons, exhibiting first at the Wakefield Bookshop, the Mortimer Brandt Gallery and then when Parsons opened her own gallery on 57th street. Reinhardt had regular solo exhibitions yearly at the Betty Parsons Gallery beginning in 1946. He was involved in the 1940 protest against MoMA, designing the leaflet that asked How modern is the Museum of Modern Art? His works were displayed regularly throughout the 1940s and 1950s at the Annual Exhibitions held at the Whitney Museum of American Art. He was also part of the protest against the Metropolitan Museum of Art in 1950 which became known as "The Irascibles."

Reinhardt's earliest exhibited paintings avoided representation, but show a steady progression away from objects and external reference. His work progressed from compositions of geometrical shapes in the 1940s to works in different shades of the same color (all red, all blue, all white) in the 1950s. Reinhardt is best known for his so-called "black" paintings of the 1960s, which appear at first glance to be simply canvases painted black but are actually composed of black and nearly black shades. Among many other suggestions, these paintings ask if there can be such a thing as an absolute, even in black, which some viewers may not consider a color at all.

Reinhardt joined the staff of PM in 1942 and he worked full-time at this daily newspaper until 1947, with time out while drafted for active duty in the U.S. Navy. While at PM he produced several thousand cartoons and illustrations most notably the series of famous and widely reproduced How to Look at Art series. Reinhardt also illustrated the highly influential and controversial pamphlet Races of Mankind (1943) originally intended for distribution to the U.S. Army, but after being banned subsequently sold close to a million copies. He also illustrated a children's book A Good Man and His Good Wife. While attending Columbia University he designed many covers and illustrations for the humor magazine Jester and was its Editor in his senior year (1934–35). In 1940 he was the designer of "The Chelsea Document", a public exhibition of five 4x8 foot panels.Other commercial art work was done "for such varied employers as the Brooklyn Dodgers, Glamour magazine, the CIO, Macy's, The New York Times, the National Council of American-Soviet Friendship, The Book and Magazine Guild, the American Jewish Labor Council, New Masses, the Saturday Evening Post, Ice Cream World, and Listen magazine. He illustrated many books such as Who's Who in the Zoo.

Having completed his studies at the New York University Institute of Fine Arts, Reinhardt became a Teacher at Brooklyn College in 1947 and taught there until his death in 1967. He also taught at the California School of Fine Arts in San Francisco, the University of Wyoming, Yale University and Hunter College, New York.

In 1967 he contributed one of 17 signed prints that made up the portfolio Artists and Writers Protest Against the War in Viet Nam organized by the group Artists and Writers Protest. Reinhardt's lithograph, known as "No War" from its first two words of text, shows both sides of an air mail post card addressed to "War Chief, Washington, D.C. U.S.A." with a list of 34 demands that includes “no napalm,” "no bombing,” “no poverty,” "no art of war," and admonitions concerning art itself, “no art in war” and “no art on war."

His writing includes comments on his own work and that of his contemporaries. His concise wit, sharp focus, and sense of abstraction make them interesting reading even for those who have not seen his paintings. Like his paintings, his writing remains controversial decades after its composition. Many of his writings are collected in Art as Art, edited by Barbara Rose, University of California Press, 1991.