The Maryland campaign (or Antietam campaign) occurred September 4–20, 1862, during the American Civil War. The campaign was Confederate General Robert E. Lee's first invasion of the North. It was repulsed by the Army of the Potomac under Maj. Gen. George B. McClellan, who moved to intercept Lee and his Army of Northern Virginia and eventually attacked it near Sharpsburg, Maryland. The resulting Battle of Antietam was the bloodiest day of battle in American history.

Following his victory in the northern Virginia campaign, Lee moved north with 55,000 men through the Shenandoah Valley starting on September 4, 1862. His objective was to resupply his army outside of the war-torn Virginia theater and to damage Northern morale in anticipation of the November elections. He undertook the risky maneuver of splitting his army so that he could continue north into Maryland while simultaneously capturing the Federal garrison and arsenal at Harpers Ferry. McClellan accidentally found a copy of Lee's orders to his subordinate commanders and planned to isolate and defeat the separated portions of Lee's army.

While Confederate Maj. Gen. Stonewall Jackson surrounded, bombarded, and captured Harpers Ferry (September 12–15), McClellan's army of 102,000 men attempted to move quickly through the South Mountain passes that separated him from Lee. The Battle of South Mountain on September 14 delayed McClellan's advance and allowed Lee sufficient time to concentrate most of his army at Sharpsburg. The Battle of Antietam (or Sharpsburg) on September 17 was the bloodiest day in American military history with over 22,000 casualties. Lee, outnumbered two to one, moved his defensive forces to parry each offensive blow, but McClellan never deployed all of the reserves of his army to capitalize on localized successes and destroy the Confederates. On September 18, Lee ordered a withdrawal across the Potomac and on September 19–20, fights by Lee's rearguard at Shepherdstown ended the campaign.

Although Antietam was a tactical draw, it meant the strategy behind Lee's Maryland campaign had failed. President Abraham Lincoln used this Union victory as the justification for announcing his Emancipation Proclamation, which effectively ended any threat of European support for the Confederacy.

The year 1862 started out well for Union forces in the Eastern Theater. George B. McClellan's Army of the Potomac had invaded the Virginia Peninsula during the Peninsula Campaign and by June stood only a few miles outside the Confederate capital at Richmond. However, when Robert E. Lee assumed command of the Army of Northern Virginia on June 1, fortunes reversed. Lee attacked McClellan aggressively at the end of June in the Seven Days Battles; McClellan lost his nerve, and his army retreated down the Peninsula. In July, Lee then conducted the northern Virginia campaign in which he outmaneuvered and defeated Maj. Gen. John Pope and his Army of Virginia, most significantly at the Second Battle of Bull Run (Second Manassas), before McClellan's corps could reinforce Pope. Lee's Maryland campaign can be considered the concluding part of a logically connected, three-campaign, summer offensive against Federal forces in the Eastern Theater.

The Confederates had suffered significant manpower losses in the wake of the summer campaigns. Nevertheless, Lee decided his army was ready for a great challenge: an invasion of the North. His goal was to reach the major Northern states of Maryland and Pennsylvania, and cut off the Baltimore and Ohio Railroad line that supplied Washington, D.C. His movements would threaten Washington, D.C., and Baltimore, so as to "annoy and harass the enemy."

Several motives led to Lee's decision to launch an invasion. First, he needed to supply his army and knew the farms of the North had been untouched by war, unlike those in Virginia. Moving the war northward would relieve pressure on Virginia. Second was the issue of Northern morale. Lee knew the Confederacy did not have to win the war by defeating the North militarily; it merely needed to make the Northern populace and government unwilling to continue the fight. With the Congressional elections of 1862 approaching in November, Lee believed that an invading army playing havoc inside the North could tip the balance of Congress to the Democratic Party, which might force Abraham Lincoln to negotiate an end to the war. He told Confederate President Jefferson Davis in a letter of September 3 that the enemy was "much weakened and demoralized."

There were secondary reasons as well. The Confederate invasion might be able to incite an uprising in Maryland, especially given that it was a slave-holding state and many of its citizens held a sympathetic stance toward the South. Some Confederate politicians, including Jefferson Davis, believed the prospect of foreign recognition for the Confederacy would be made stronger by a military victory on Northern soil, but there is no evidence that Lee thought the South should base its military plans on this possibility. Nevertheless, the news of the victory at Second Bull Run and the start of Lee's invasion caused considerable diplomatic activity between the Confederate States and France and the United Kingdom. Additionally, generals Braxton Bragg and Edmund Kirby Smith in the Western Theatre outmaneuvered Don Carlos Buell to reach the border state of Kentucky from eastern Tennessee through the Battle of Richmond which coincided with Confederate victories in the East.