Andre was born in Quincy, Massachusetts, and after studying art in the States and in Europe became an intelligence officer with the United States Army in North Carolina. In 1957 he moved to New York City to work as an editor, and in the early 1960s worked as a railroad conductor on the Pennsylvania Railroad. His first solo show came in 1965.
Andre's work has been typified by the use of natural or simple commercially available materials, such as bricks, metal plates or concrete blocks, stacked or arranged side by side in simple patterns. One of his first distinctive works is Cedar Piece, which consists pieces of wood stacked on top of one another in a tall column. Andre cited the wooden sculptures of Constantin Brancusi as an influence in this and similar works.
A little later in the 1960s, Andre began to make so-called "scatter pieces", which consisted of pieces of a particular material arranged, apparently at random, on the floor. Later came pieces such as 10 x 10 Altstadt Copper Square (1967), a ten by ten arrangement of 100 copper tiles on the floor. Andre has made a number of similar pieces, sometimes using just one kind of metal, sometimes using two and arranging them in a chessboard pattern. The viewer is free to walk over these pieces, if they so choose.
Andre made a series of works called Equivalents, all of them arrangements of 120 identical bricks in simple patterns. In 1972 the Tate Gallery in London bought his Equivalent VIII (1966), which four years later was the subject of an outcry from parts of the media, who accused them of wasting public money.
Since the earliest time in his career, Andre has also produced concrete poetry. Many have seen the arrangement of words on the page in these poems as reflecting the arrangement of units on the floor in his sculptures.