President Lincoln was disappointed in McClellan's performance. He believed that McClellan's overly cautious and poorly coordinated actions in the field had forced the battle to a draw rather than a crippling Confederate defeat. The president was even more astonished that from September 17 to October 26, despite repeated entreaties from the War Department and the president himself, McClellan declined to pursue Lee across the Potomac, citing shortages of equipment and the fear of overextending his forces. General-in-Chief Henry W. Halleck wrote in his official report, "The long inactivity of so large an army in the face of a defeated foe, and during the most favorable season for rapid movements and a vigorous campaign, was a matter of great disappointment and regret." Lincoln relieved McClellan of his command of the Army of the Potomac on November 5, effectively ending the general's military career. He was replaced on November 9 by General Burnside.

The results of Antietam also allowed President Lincoln to issue the preliminary Emancipation Proclamation on September 22, which gave Confederate states until January 1, 1863, to end their rebellion or else lose their slaves. Although Lincoln had intended to do so earlier, Secretary of State William H. Seward, at a cabinet meeting, advised him to wait until the Union won a significant victory so as to avoid the perception that it was issued out of desperation.

The Union victory and Lincoln's proclamation played a considerable role in dissuading the governments of France and Britain from recognizing the Confederacy; some suspected they were planning to do so in the aftermath of another Union defeat. When emancipation was linked to the progress of the war, neither government had the political will to oppose the United States, since it linked support of the Confederacy to support for slavery. Both countries had already abolished slavery, and the public would not have tolerated the government militarily supporting a sovereignty upholding the ideals of slavery.