[2] He moved to Liberty, Missouri, in 1847 and St. Joseph the following year, beginning as a store clerk before taking up surveying and serving as the city engineer.

He commanded the First Military District of Missouri, which covered the swampy southeastern quarter of the state from St. Louis to the Mississippi River.

On October 15, 1861, Thompson led a cavalry attack on the Iron Mountain Railroad bridge over the Big River near Blackwell in Jefferson County.

After briefly commanding rams in the Confederate riverine fleet in 1862, Thompson was reassigned to the Trans-Mississippi region.

There, he engaged in a number of battles before returning to Arkansas in 1863 to accompany Gen. John S. Marmaduke on his raid into Missouri.

Thompson was captured in August in Arkansas, and spent time in St. Louis' Gratiot Military Prison, as well as at the Fort Delaware and Johnson's Island prisoner-of-war camps ("Poor old Jeff, how my heart went out to him; he a prisoner and his devoted wife in a madhouse", Major Lamar Fontaine wrote later).

In early 1862 at New Orleans, a side-wheel river steamer was converted to a "Cottonclad" ram and named after Thompson.

Thompson was sent up the Mississippi that April to join the River Defense Fleet in Tennessee waters, seeing its first action at Plum Point Bend.