He successively served at Fort Monroe in Virginia, Carlisle Barracks in central Pennsylvania, and then in Zachary Taylor's occupation army in Texas in 1845 before returning to the academy as assistant professor in 1846.

Reynolds's 10th Indiana Volunteer regiment was sent to western Virginia, where it played a decisive role repulsing Confederates under Robert E. Lee at Cheat Mountain.

Although promoted to brigadier general, Reynolds resigned in January 1862 and resumed training Indiana regiments at Camp Morton until November 1862 without a commission.

After serving as the army's chief of staff before Chattanooga, Reynolds was transferred to the Gulf of Mexico, where he led a division of XIX Corps that garrisoned New Orleans, Louisiana.

When military rule in Texas ceased in 1870, Reynolds again returned to frontier garrison duty, and was made the Colonel of the 3rd United States Cavalry Regiment.

Reynolds participated the Black Hills War, of 1876-1877, and led the Big Horn Expedition out of Fort Fetterman, Wyoming Territory, on March 1, 1876 in search of "hostile" Lakota Sioux and Northern Cheyenne Indians under Sitting Bull and Crazy Horse.