John Palmer Usher was born January 9, 1816 or January 18, 1818 in Brookfield, Madison County, New York. He studied law under Henry Bennett in New Berlin, New York and was admitted to the bar in 1839. He soon thereafter moved to Terre Haute, Indiana to open a law practice. A circuit lawyer in the 1840s and 1850s in both Indiana and Illinois, he became acquianted at that time with Abraham Lincoln.

Usher was elected to the Indiana state legislature in 1850, serving one term. He unsuccessfully ran for a U.S. House of Representatives position as a Republican in 1856 and participated in Lincoln's 1860 presidential campaign. In 1861 he was appointed the Indiana Attorney General, but he soon resigned this position to become Assistant Secretary of the United States Department of the Interior.

Secretary of the Interior Caleb Smith resigned his position in December 1862. On January 3, 1863, Usher was appointed his replacement, a role he held until his official resignation on May 15, 1865.

Usher eventually moved his family to Lawrence, Kansas after resigning from his post in Washington, D.C. and considering several other towns in Kansas in which to live. He built a home at 1425 Tennessee Street in Lawrence, completing it in 1873. He became general solicitor for the Union Pacific Railway, Eastern Division and actively promoted the building of the railroad west of Kansas City. He argued several significant cases for the railroad, many regarding land grants or relations with other railroads. He also served as mayor of Lawrence, KS for one term.

John Palmer Usher married Margaret A. Patterson, the daughter of Arthur and Margaret (Chambers) Patterson, on January 26, 1844 in Rockville, Indiana. They had four sons: Arthur Patterson, John Palmer, Linton Joseph, and Samuel Chambers. John Palmer Usher died from cancer in 1889. His wife died in 1911, and together they were buried in Oak Hill Cemetery in Lawrence. Soon after Mrs. Usher's death, the family sold the house to the Alpha Nu chapter of the Beta Theta Pi fraternity, whose members moved in in 1913.