Upon graduation, he was commissioned a brevet second lieutenant in the 3rd U. S. Artillery at Fort McHenry. Between 1842 and 1845 he was assigned to St. Augustine, Florida, and Fort Moultrie, South Carolina. He was then assigned to Zachary Taylor's army at Corpus Christi, Texas, for service in the Mexican-American War.
Serving with the artillery in the War with Mexico, he performed gallantly and efficiently and was awarded two battlefield brevet promotions. He was promoted to captain for gallantry at Monterrey, and to major at Buena Vista, where his guns prevented the Mexican cavalry from outflanking the American left flank.
After the war with Mexico, Reynolds was assigned to posts in Maine, New Orleans, and New York. Then, in 1855, he was sent to Fort Orford, Oregon, where he participated in the Rogue River Wars of 1856, and the Utah War with the Mormons in 1857 and 1858. From 1860 to June 1861, he was the Commandant of Cadets at West Point. In August 1861, Reynolds was promoted to Brigadier General. At this time, Reynolds became engaged to Katherine May Hewitt. Reynolds was a Protestant and Hewitt a Catholic. Because of this difference in religion, the engagement was kept a secret and Hewitt's parents knew nothing of it until after Reynolds's death
At the beginning of the Civil War, Reynolds served under General McClellan in the battles of the Virginia Peninsula, including the second Battle of Bull Run and the Battle of Fredericksburg. On July 1, 1863, at Gettysburg, General Reynolds was commanding the "left wing" of the Army of the Potomac, which consisted of the 1st, 3rd and eleventh Corps, and Brigadier General John Buford's Cavalry Division. On this first day of the Battle of Gettysburg, while Reynolds was directing his forces against the oncoming Confederate army, he was shot by a Confederate sharp shooter and fell dead from his horse.
History has recorded that General John Fulton Reynolds was a person of great character, honest, energetic, and a general of distinguished ability. He performed his duties with zeal and fidelity. He was respected and admired by this troops and all who knew him.