He moved to Leavenworth, Kansas in 1861 and engaged in the transportation of military supplies to the various posts on the plains. He was engaged in the building of railroads, especially the Missouri River and Kansas Central Railroad. He was elected as a Republican to the U.S. Senate and served from March 4, 1871, to March 24, 1873, when he resigned. From 1877 to 1897, he manufactured wagons and carriages, and from 1897 to 1915 he was president of the First National Bank of Leavenworth.
Caldwell died in Kansas City, Missouri in 1917. He is interred at Mount Muncie Cemetery, Leavenworth.