Harry Hueser was born in Lee County, Iowa on July 2, 1890 to Lewis L. Hueser and Anna Gang. He was raised in Fort Madison, Iowa, Chillicothe, Illinois, and Chicago, Illinois. His father was a railroad engineer who ran the local #576 between Chillicothe and Streator, Illinois on the Santa Fe Railroad. He had one brother.

Hueser was interested in art during high school, and entered the University of Illinois to study architecture in 1911. He dropped out after one semester, but continued his education at the Academy of Fine Arts in Chicago and the American College of Physical Education. He worked as a commercial artist and freelancer and taught occasionally at the Academy of Fine Art. Hueser designed advertising and sign campaigns for Sanka Coffee, Marshall Field & Company, and the Comet train.

Hueser resided in mental hospitals between 1931 and 1955, and lived in a nursing home during his later years. While living there, he came to know the manager of the nursing home, Mary Ann Travis, who supplied him with drawing supplies and encouraged him to continue drawing.

Hueser was married to Edith Marjorie Paradise. The couple had one adopted daughter, Viola Jean. Harry Hueser passed away in 1978.