Frank Mechau grew up in Colorado Springs, Colorado and studied at the University of Denver (1923-24) and then at the Art Institute of Chicago (1924-25.) He earned money to finance his education as a cattle hand and a prize fighter.

Mechau spent a number of years in New York and in europe before his return to Denver in 1931 where he began instructing.

In 1934, he was the recipient of a Guggenheim fellowship. That same year, he began receiving commissions for murals from the Works Progress Administration/Federal Art Project. Two years later one of his Post Office murals, "Dangers of the Mail" received national attention. The controversial image depicted an overtuned stagecoach with American Indians murdering white men and scalping nude white women. Mechau commented on the mural saying "No Artist ever wished to be considered an ethnologist, my intention was to create an imaginative reconstruction of a massacre."

Mechau taught at the Colorado Springs Fine Arts Center (Broadmoor Academy) in 1937 and 1938 and later served as director of art classes at Columbia between 1939 amd 1943.

He worked as an artist correspondent for Life Magazine beginning in 1944.