July 21, 1861: Union Gen. Irvin McDowell marched out of Washington, D.C. into Virginia, intent on seizing the Confederate capital of Richmond and putting an end to the war. But most of McDowell’s men were inexperienced, 90-day volunteers, who’d joined in expectation of a brief conflict and had little idea what was in store for them. They came up against a force commanded by Gen. Pierre G. T. Beauregard, which was defending a critical railroad junction at Manassas, Virginia. When McDowell’s forces attacked, the Confederates initially were driven back, but reinforcements soon arrived, including a brigade led by then-Brig. Gen. Thomas J. Jackson, who would earn the nickname “Stonewall” for his tenacity in holding ground.

In the war’s first major battle, Union forces were routed, with an estimated 2,896 killed, wounded, missing or captured. The victorious Confederates suffered 1,982 casualties of their own. As each side counted their dead, it became evident that the struggle ahead would be longer and more grisly than Americans had expected.

February 11-16, 1862: One of the first major Union victories was then-Brig. Gen Ulysses S. Grant’s capture of Fort Donelson, located along the Cumberland River in Tennessee. The Confederates initially repulsed an attack by union gunboats, and planned a bold counterattack against the Union troops to clear a path for escape. The Confederates seemed on the verge of success when they halted and retreated to their fortifications. That gave Grant time to figure out a weak point in the Confederate line—and attack it.

Confederate generals Gideon Pillow and John B. Floyd fled, leaving behind 13,000 soldiers, who waved a white flag above their fortifications. When the rebels asked for terms of surrender, Grant replied that no terms “except unconditional and immediate surrender” would be acceptable. This earned him the nickname “Unconditional Surrender.”

The victory, along with the capture of nearby Fort Henry, opened up the state of Tennessee to Union invasion, and helped turn Grant into a national hero.

September 17, 1862: Gen. Robert E. Lee and his Army of Northern Virginia invaded Maryland in an attempt to knock the Union back on its heels. President Abraham Lincoln sent Maj. Gen. George McClellan and his Army of the Potomac to stop him.

The two forces initially collided at dawn in a cornfield in Sharpsburg, Maryland, where their movements were obscured by the tall corn stalks as they fired upon one another. The battle eventually shifted to a stone bridge along Antietam Creek, where Union troops had to storm a Confederate position three times before finally capturing it. An estimated 22,717 men on both sides were killed, wounded, captured or went missing.

Though the battle ended in a stalemate, the Union had stymied Lee’s invasion. That gave Lincoln enough confidence to issue the Emancipation Proclamation, which redefined the Civil War from a struggle to preserve the Union to one focused on ending slavery. Meanwhile, photographs by Alexander Gardner of bodies strewn on the battlefield, displayed in Matthew Brady’s gallery in New York, brought home to northerners the brutal cost of the war.

May 1-6, 1863: Lee achieved one of his greatest triumphs at Chancellorsville, Virginia, where he divided his forces and sent Lt. Gen. Thomas J. “Stonewall” Jackson to force his way through a rough forest to outflank units led by Union Gen. Joseph Hooker. After several days of fighting, the Union troops were forced to retreat. By the end, Hooker had suffered more than 17,000 casualties to Lee’s nearly 13,000.

It was a decisive victory for Lee and the South—but it came at a high cost. Among Lee’s casualties was Jackson, one of the most capable Confederate officers. Jackson was wounded by friendly fire and died four days after the battle.

May 18-July 4, 1863: Confederate President Jefferson Davis saw Vicksburg, Mississippi, a fortress port and railroad hub along the Mississippi River, as “the nail head that holds the South’s two halves together.” That made it imperative for the Union to take what was known as the Gibraltar of the Confederacy.

In mid-May, Grant sent his forces to attack the city several times, but they were unable to penetrate the Confederates’ defenses. That forced him to settle into a long siege, in which he bombarded Vicksburg with artillery and fire from Union gunboats, and forced Confederate defenders and the civilian population to endure hunger and illness. Many hid in man-made caves dug under the city.

In June, Grant tried one last assault, deploying miners to tunnel under the Confederate fortifications and plant explosives that carved out a 12-foot-deep crater. But the Union forces were unable to advance out of it and had to retreat. By July, Confederate Lt. Gen. John C. Pemberton and his 29,000 men couldn’t hold out any longer, and had to surrender to Grant.

The victory gave the Union control of the critical supply line of the entire Mississippi River. And the Confederacy was split.

July 1-3, 1863: Lee again invaded the Union in the summer of 1863 in hopes that he could beat the Union on its own soil, threaten Washington, D.C., and force Lincoln to agree to a peace treaty.

With Virginia devastated by the war, he also desperately needed supplies for his soldiers. Lee’s Army of Northern Virginia was pursued by Union forces led by Maj. Gen. George Meade, who caught up with them in Pennsylvania and confronted the Confederates at Gettysburg, in what was one of the most fateful battles in history.

Initially, the Confederates drove Union troops from fields west and north of the town, but they failed on the second day to break the Union line. On July 3, Lee attacked the center of the Union forces at Cemetery Ridge, south of Gettysburg. After two hours of shelling, Confederate Gen. George Pickett led two brigades in an assault on the Union position. Pickett’s Charge, as it became known, turned into a disaster, with the Confederates suffering 60 percent casualties. Lee was forced to retreat and abandon his invasion.

July 22, 1864: Near the end of the war, a trio of Union armies, led by Gen. William T. Sherman converged upon Atlanta, where they were met outside the city by a desperate Confederate counterattack that failed.

The Battle of Atlanta was the bloodiest part of Sherman’s March through Georgia, costing the Union 3,700 casualties, while the Confederates lost 5,500 men. Sherman’s forces continued their advance and finally surrounded the city, besieging it for the entire month of August.

Finally, on September 1, Confederate Lt. Gen. John Bell Hood, a veteran of Antietam and Gettysburg who had lost his leg at the Battle of Chickamauga, gave up and abandoned the city, allowing Sherman’s forces to enter.

The capture of Atlanta crippled the Confederate war effort. For Lincoln, who faced a difficult election in 1864 against one of his former generals, George B. McClellan, the victory provided a lift at the polls, helping him win and pursue the war to its conclusion.