In Pennsylvania, at the Battle of Gettysburg, Lee aimed to triumph in a conflict in the north. A Confederate triumph in the north might open the door to peace talks to terminate the conflict. The battle lasted for days as the two forces faced one other on two heights. The Confederate military command was less strong without Stonewall Jackson. Due to ineffective military leadership and several tactical errors that resulted in high deaths, the south lost the battle of Gettysburg. Numerous Southern soldiers were killed during the historic Pickett's charge, which involved the Confederates marching uphill under Union fire. Attempts by the southern cavalry to attack the Union forces from behind were also thwarted by Union soldiers.

The Battle of Gettysburg resulted in a significant death toll. In actuality, it was the Civil War combat with the most fatalities. Over 51,000 individuals died, including 28,063 Confederates and 23,049 Union forces. The battleground is still accessible today. The location of many graves is a national military park. The famous Gettysburg Address was delivered by Abraham Lincoln on the grounds of this cemetery.

The Battle of Gettysburg dealt a significant blow to southern morale. The high number of casualties was heartbreaking. Thousands of Confederate officers were lost and could not be replaced so late in the war. The Confederate economy was also harmed, and the government opted to sell bonds, further harming the economy.

On July 4, 1863, one day after the conclusion of the Battle of Gettysburg, the Union was triumphant at Vicksburg after a six-month siege to gain control of the Mississippi River. The Union had the goal of controlling the Mississippi in order to divide the Confederacy. Isolating Texas and New Mexico would weaken the Confederacy. Union forces attempted to take over Vicksburg during the siege headed by Ulysses S. Grant, a future US president. However, it proved challenging due to the city's location along the river, which was surrounded by wetlands. After numerous fruitless attempts, gunships assisted battling forces in getting closer to the city. From within the city, Confederates fought to shoot at Union soldiers, and by July, Vicksburg had run out of supplies and surrendered. During the six-month siege, there were 37,273 casualties. There were 4,910 Union soldiers and 32,363 Confederates among them.

Although the war would go another two years, the Confederacy's defeat at Vicksburg signalled the beginning of the end. The Union gained hope after the victory at Gettysburg, which was swiftly followed by the victorious siege of Vicksburg on July 4th of all days. With Mississippi River control, the Confederacy was now divided, with Texas and New Mexico isolated.

On January 1, 1863, President Abraham Lincoln issued an edict freeing the slaves of the Confederate states in rebellion against the Union.

Prior to the outbreak of the American Civil War, many Northerners and officials were primarily concerned with preventing the spread of slavery into western territories that would eventually acquire statehood inside the Union. However, with the secession of the Southern states and the subsequent outbreak of the Civil War, Northern tolerance of Southern slavery appeared to serve no constructive political purpose. As a result, emancipation went from a distant possibility to a near-term one. Lincoln had stated that he intended to save the Union as best he could, whether by protecting slavery, eliminating it, or destroying part of it and preserving the rest. He issued his proclamation shortly after the Battle of Antietam (September 17, 1862), calling on the rebelled states to return to their allegiance before the next year, or their slaves would be deemed free men. On January 1, 1863, no state returned, and the dreaded declaration was issued.

Lincoln could not issue such a statement as president; as commander in chief of the United States troops and ships, he could only issue orders for territory within his lines, but the Emancipation Proclamation extended solely to land outside his lines. As a result, the question of whether the proclamation had any force has been raised. It can fairly be interpreted as a proclamation of the policies that would lead the army as well as a declaration of freedom that would take effect as the lines advanced. In any case, this was the exact result.

Its international significance was far bigger. The closure of the world's source of cotton supply had been a general disaster, and the Confederate government and people had consistently expected the English and French governments to interfere in the war. The transformation of the conflict into a crusade against slavery rendered European engagement impossible.

The Emancipation Proclamation did more than elevate the conflict to the level of a human-liberation crusade. It had a significant practical impact since it permitted the Union to enlist Black soldiers. Blacks responded in large numbers to this call to join the army, with approximately 180,000 enlisting during the duration of the war. Lincoln could state in a letter to James C. Conkling on August 26, 1863, that "the emancipation program, and the use of colored troops, represent the hardest blow yet inflicted to the insurrection."

Lincoln informed portrait painter Francis B. Carpenter in February 1865, two months before the war ended, that the Emancipation Proclamation was "the central act of my government, and the greatest event of the nineteenth century." To Lincoln and his fellow citizens, the proclamation had struck the proverbial deathblow to slavery in the United States, a fate that was officially cemented by the adoption of the Thirteenth Amendment in December 1865.