Crabtree was born in Heyburn, Idaho on June 8, 1912. His parents were Reverend Ellis and Mabel G. Crabtree and they lived on 140 acres in the Salmon River Valley. In 1917, the Crabtrees moved to a 10-acre plot outside of Twin Falls and established a garden and pickle business. Crabtree lived a close life to his parents and two sisters in the Twin Falls community.

Don finished high school in Twin Falls in 1930 and worked for the Idaho Power Company. He then decided to move to California where he enrolled in Long Beach Junior College in the mid-1930s, intending to major in geology and paleontology. His interest in those topics and in prehistoric archaeology had developed during a childhood and youth spent exploring south-central Idaho. Crabtree tried flintknapping, but at the time, it was not his primary focus.

Crabtree was a very active person and was not happy with just studying and after one term at Long Beach Junior College, he dropped out and went the rest of the way by himself. Even though he was self-conscious about his lack of education and disliked public speeches, he was recognized internationally as one of the most thoughtful and provocative students of prehistoric technologies.

Crabtree began working in paleontological laboratories and by the late 1930s he was the preparator in the vertebrate paleontology laboratory at the University of California, Berkely. He worked under the direction of Charles Camp and Ruben Stirton and did summer fieldwork in Nevada and California. Crabtree became acquainted with Alfred L. Kroeber and E.W. Gifford of the Lowie Museum at Berkeley and in the late 1930s, worked as a technician in the anthropology program while he further developed his flintknapping skills. He also conducted knapping demonstrations for scholars and students at Berkeley and occasionally for museum visitors.

In 1939, Crabtree was diagnosed with cancer and returned home to his parents' home during what were considered to be his last days. However, massive cobalt treatments and his mother's and his indomitable patience through months on intensive care, led him to recovery. He spent his recuperation period, when his mobility was limited and as he was trying to regain muscular strength, flintknapping — making arrowheads, spearpoints and eccentric lithic forms by the hour.

What had been a virtuoso performance until that time became a confirmed craft and art, all the time conducted amidst a personal search for information about lithic mechanics, systems of efficient core reduction and the significance of variations among the newly identified paleo-Indian points from the Plains and Southwest.

In the spring of 1941, fully recovered and with a year of concentrated flintknapping behind him, Crabtree was invited to demonstrated knapping techniques at the American Association of Museums' annual meeting in Columbus, Ohio. As a result of that demonstration, he was employed for Shetrone, replicating eastern lithic artifacts. Crabtree was also called upon as an advisor in lithic studies to the University of Pennsylvania, where he was associated with Edgar B. Howard and the Clovis type site and other Blackwater Draw materials. It was during this period that he had his first "hands on" acquaintance with the Folsom materials, one of his lifelong fascinations, when Frank H. Roberts of the Smithsonian Institution called Crabtree in as a consultant in the analysis of the Lindenmeier Folsom collection.

Everything was going right in the fall of 1941; the cancer was in remission, Crabtree has employment doing that in which he was most interested (working with stone tools), and he was becoming recognized as one of the leading students of that subject by major archaeological institutions. Then the United States entered World War II, the Lithic Laboratory was discontinued, and Crabtree returned to California to join the war effort.

From 1941 until the late 1950s, Crabtree's involvement with flintknapping was only as an avocation. He spent the war years in Long Beach where he worked as a coordination engineer for Bethlehem Steel Company, which built the ships for the Pacific effort. There he met his beloved wife, Evelyn Josephine Meadows; they married in Long Beach in 1943. Their relationship was a strong and close interdependency, she was serving as his housekeeper, traveling companion, secretary and editor, and always his closest confidant. They never had children of their own, rather "adopting" the young students who flocked around Crabtree to learn and consult. Evelyn's health problems were also significant; she had lost a lung to tuberculosis when she was a young woman and spent her last years in a long fight against cancer. Their 33 years together were a true partnership, and one did not know Don Crabtree unless one knew Evelyn.

Following World War II, the Crabtrees returned to Twin Falls. They purchased the big family home from Don's parents, and he soon was a real estate salesman in a booming postwar market. Evelyn was a manager of a large savings and loan institution, where she dealt in real estate and more general financial matters. They eventually sold the large house and bought a small place out in the country just east of Twin Falls and over the years they added rooms and a shop until finally they had a modest but complete lithic laboratory and guest facility.

Crabtree was employed from 1952 until 1962 as a county supervisor for the U.S. Department of Agriculture's Agricultural Stabilization and Conservation Service (ASCS) in Twin Falls, spending much of his time in aerial photo interpretation of soil conservation problems. He continued to read voraciously, to keep up with archaeological publications, and to demonstrate flintknapping to local school and youth groups. He also continued his investigations into the archaeology of southern Idaho, particularly its prehistory. He was locally quite well-known for his knapping skills and knowledge, and that local fame led him to a reentry into the scholarly world of lithic studies in 1958.

In 1958, Earl H. Swanson Jr., who established the first major archaeological program at the Idaho State University in Pocatello, Idaho, introduced himself to Crabtree after hearing from local people about the flintknapper with an amazing skill and major regional archaeological collection. Crabtree and Swanson shared a deep friendship and it lasted until Swanson's untimely death in 1975. Swanson's international credentials and participation in the "early man" network of American archaeologists gave Crabtree access to research monies and forums that he would not have entered on his own, and Swanson never hesitated to do whatever he could to provide Crabtree with that access by extension.