Cressman was born outside of Pottstown, Pennsylvania, the son of a physician. He was ordained an Episcopal priest in 1923, but feeling doubts about his vocation, began studying sociology and anthropology at Columbia University in New York. He received his Ph.D. from Columbia in 1928, and that same year, he left the priesthood.
In 1929, he took a position as Professor of Sociology at the University of Oregon. The Department of Anthropology was founded by him six years later. His first hire for the department was Homer Barnett. Cressman was the chair of the department from 1935 until his retirement in 1963.
His most significant discovery came in 1938, when he discovered a pair of perfectly preserved shredded sagebrush bark sandals at Fort Rock in Oregon that were radiocarbon dated from 10,500 to 9,300 years old, making them the oldest footwear ever discovered.
His autobiography A Golden Journey: Memoirs of an Archaeologist was awarded the 1989 Oregon Book Award for literary nonfiction.
Cressman married anthropologist Margaret Mead in 1923; the couple divorced in 1927. He married Dorothy Cecelia Loch in 1928. They had one daughter and were married for 49 years, until her death in 1977.