The armies of the Union and the Confederacy were commanded by a large number of men.

The Union

Joseph Hooker (1814–79) was known by the nickname “Fighting Joe” Hooker, which he greatly disliked. He led the Union attack at Antietam and was wounded, but he recovered to command a corps in the Battle of Fredericksburg just three months later. He was appointed to command the Army of the Potomac in January 1863. Hooker lost to Lee in the Battle of Chancellorsville in May 1863. He was removed from the Army of the Potomac in June 1863 just before the Battle of Gettysburg. Hooker saw combat in the Battle of Chattanooga and the siege of Atlanta.

George G. Meade (1815–77) saw action at Mechanicsville, Gaines's Mills, and White Oak Swamp, where he was badly wounded. He returned to lead his brigade in the Second Battle of Manassas and the Battle of Antietam. Meade replaced Hooker as commander of the Army of the Potomac on June 28, 1863 — just in time to lead it during the Battle of Gettysburg.

George Henry Halleck (1815–72) was appointed major general in charge of the newly formed Military Department of Missouri and was later placed in command of the Departments of Kansas and Ohio. He took command of Union forces after the Battle of Shiloh, with instructions to crush Beauregard's army but acted with such hesitancy that Beauregard was able to retreat. Lincoln appointed Halleck general-in-chief of all the armies of the North, where he proved more skilled as an administrator than commander.

Philip Sheridan (1831–88) was one of the youngest commanders to serve in the Civil War. He fought in numerous battles in both the east and the west but was most famous for his scorched earth policy during his Shenandoah Valley Campaign of 1864–65.

Ambrose Everett Burnside (1824–81) raised a brigade that fought well at the First Battle of Manassas and was instrumental in the capture of several vital Southern coastal positions some months later. Promoted to major general, Burnside twice refused offers to take over the Army of the Potomac from McClellan, with whom he was friends, but he finally accepted when Lincoln offered him the position in 1862. His tenure there proved short-lived, if bloody and demoralizing for the North.

George Custer (1839–76) is remembered more for his last stand at Little Bighorn in 1876 than his participation in the Civil War. At twenty-three, he became the youngest general in the Union army. He distinguished himself at Gettysburg with a series of daring frontal attacks that held back Jeb Stuart's advance on the Union flank and rear. Custer and Stuart met again at the Battle of Yellow Tavern in 1864.

Custer was present during Lee's surrender to Grant at the Appomattox Court House, Virginia. Custer and his cavalry had played an important role in forcing Lee's retreat to Appomattox, and Philip Sheridan thanked Custer by giving him the table upon which the surrender had been signed.

The Confederacy

Nathan Bedford Forrest (1821–77) rose from private to lieutenant general in the Confederate army and became one of the war's most feared cavalry commanders because of his lightning raids on enemy camps. His cavalry successfully covered the Confederate withdrawal following the Battle of Shiloh, even though Forrest was seriously wounded. He saw combat at the battles of Murfreesboro and Chickamauga, among many others. Forrest led the extremely controversial capture of Fort Pillow, Tennessee, in which his men were accused of slaughtering more than 200 unarmed troops, primarily black soldiers who had already surrendered.

Albert Sidney Johnston (1803–62) was a skilled commander who was considered the equal or superior of Lee early in the war. He commanded in the west and managed to establish a bridgehead in Kentucky to protect Tennessee from a Union offensive. This line broke when Grant captured Fort Donelson in February 1862. Johnston was killed two months later at the Battle of Shiloh.

John Bell Hood (1831–79) fought well in a number of battles, including the Seven Days Battles, Second Manassas, and Antietam. He was wounded at Gettysburg and lost his right leg in the Battle of Chickamauga. Eventually he took over the Army of the Tennessee from Johnston in an attempt to force back Sherman's thrust into Georgia.

Braxton Bragg (1817–76) commanded the coast between Pensacola and Mobile during the first summer of the war and was promoted to major general of the regular army in September 1861. Bragg served under Johnston as chief of staff at the Battle of Shiloh. He was promoted to commander of the Army of the Mississippi in June 1862, replacing Beauregard. Bragg had initial successes in Kentucky but lost the opportunity for more gains by wasting time trying to set up a secessionist government in Frankfort. He commanded at the battles of Murfreesboro, Chickamauga, and Missionary Ridge. He was favored by Jefferson Davis, which explains why he lasted so long in command, but he was generally disliked by his superiors as well as those who served under him. Bragg showed flair as a military tactician but also demonstrated potentially fatal indecision on the battlefield.

James Longstreet (1821–1904) graduated from West Point in 1842. Joining the Confederate army in 1861, he rose quickly and served mainly under Lee, who called Longstreet his “warhorse.” Longstreet rose to the position of lieutenant general by 1862. He commanded a corps at Second Manassas, the right wing of Lee's army at Antietam, and a corps again at Gettysburg. He led his corps west in late summer 1863 to lend weight to the Confederates during the Battle of Chickamauga. By spring of 1864, he was with Lee again fighting Grant's army and was wounded at the Battle of the Wilderness.