Willits was principal of the Michigan State Normal School at Ypsilanti from 1883 to 1885. He served as president of the State Agricultural College from 1885 to 1889 where he inaugurated the school's mechanical engineering program and secured state funding for its initial building. In Benjamin Harrison's administration, he served as the first Assistant U.S. Secretary of Agriculture under Jeremiah McLain Rusk from March 23, 1889 to December 31, 1893. In 1890 he established the policy that all research by the Department would be mission-oriented to a practical objective, and encouraged USDA employees to look beyond the seed and plant distribution program which had previously been the main activity of the Department. This reorientation led to the creation of additional divisions within the USDA during the 1890s.