Donald Crews was born in Newark, New Jersey, in 1938. He had an older brother, Asa who became Beth Israel Hospital's first African-American intern, and two sisters. His mother worked as a seamstress, and his father worked at the railroad, and several other odd jobs. For the summers he would travel down to rural Florida to stay with his grandmother, who he called "Bigmama". The difference between the big city and the farm caused him to create two, massively different types of art later on in his life.

From a young age, his talent for drawing was encouraged by his family and his teachers. When he got into high school, one of his teachers became a mentor to him, and personally made sure that he got into art school.

He graduated from Cooper Union for the Advancement of Science and Art in New York City in 1959, and married another graduate, graphic artist Ann Jonas. He was drafted into the army in 1963, and sent to Frankfurt, Germany. Their first daughter, Nina was born in Germany, and their second was born a year later in New York.

While in Germany, he worked on several pieces for his portfolio, including the book We Read: A to Z. After several suggestions from friends, he submitted it, and it was published by Harper & Row (now HarperCollins). The book relied on abstract ideas, rather than the clichés that were usually associated with ABC books. One classic example is the entry for the letter C: "Cc, corner: where the yellow is" is illustrated with a yellow square in the far corner of a red page in the book.

He created several other books over the next few years, but it was 1979's "Freight Train" that won him a Caldecott Honor and the respect of other artists in the field. He won another Caldecott Honor the next year for "Truck". Several other transportation themed books followed, such as "School Bus" (1984), "Flying" (1986), and "Sail Away" (1995). His memories from his summers in Florida first appeared in "Bigmama's" and later in "Shortcut". These stories are vastly different from his previous works, in that they focus on humans, and tell a more linear story.

Donald and his wife currently live in the state of New York in an old, restored farmhouse overlooking the Hudson River and the Catskill Mountains.