In the early hours of July 3, the Union forces in the Twelfth Army Corps successfully repelled a Confederate attack on Culp's Hill following a seven-hour battle, and re-established their fortified position. Despite believing that his men were on the verge of victory the day before, General Lee decided to order an attack on the Union center at Cemetery Ridge. He sent three divisions, preceded by an artillery barrage, to attack the Union infantry positions that were dug in about three-quarters of a mile away. The attack, also known as "Pickett's Charge," was led by George Pickett and involved fewer than 15,000 troops.

Although General Longstreet voiced objections, General Lee was determined to proceed with the attack. At around 3 p.m., after a barrage from about 150 Confederate guns, the attack was launched. Union infantry opened fire on the advancing Confederate soldiers from behind stone walls, while regiments from Vermont, New York, and Ohio attacked both flanks of the Confederate forces. The Confederates were trapped and suffered heavy losses; only about half of them survived, and Pickett's division lost two-thirds of its men. The survivors retreated to their starting position, while Lee and Longstreet scrambled to fortify their defense line after the failed assault.