Grant's crossing of the James altered his original strategy of attempting to drive directly on Richmond, and led to the siege of Petersburg. After Lee learned that Grant had crossed the James, his worst fear was about to be realized—that he would be forced into a siege in defense of the Confederate capital. Petersburg, a prosperous city of 18,000, was a supply center for Richmond, given its strategic location just south of the capital, its site on the Appomattox River that provided navigable access to the James River, and its role as a major crossroads and junction for five railroads. Since Petersburg was the main supply base and rail depot for the entire region, including Richmond, the taking of Petersburg by Union forces would make it impossible for Lee to continue defending the Confederate capital. This represented a change of strategy from that of Grant's Overland Campaign, in which confronting and defeating Lee's army in the open was the primary goal. Now, Grant selected a geographic and political target and knew that his superior resources could besiege Lee there, pin him down, and either starve him into submission or lure him out for a decisive battle. Lee at first believed that Grant's main target was Richmond and devoted only minimal troops under Gen. P.G.T. Beauregard to the defense of Petersburg as the siege of Petersburg began.

The Siege of Petersburg consisted of nine months of trench warfare in which Union forces commanded by Lt. Gen. Ulysses S. Grant assaulted Petersburg unsuccessfully and then constructed trench lines that eventually extended over 30 miles (48 km) from the eastern outskirts of Richmond, Virginia, to around the eastern and southern outskirts of Petersburg. Petersburg was crucial to the supply of Confederate Gen. Robert E. Lee's army and the Confederate capital of Richmond. Numerous raids were conducted and battles fought in attempts to cut off the Richmond and Petersburg Railroad. Many of these battles caused the lengthening of the trench lines.

Lee finally gave into the pressure and abandoned both cities in April 1865, leading to his retreat and surrender at Appomattox Court House. The siege of Petersburg foreshadowed the trench warfare that was common in World War I, earning it a prominent position in military history. It also featured the war's largest concentration of African-American troops, who suffered heavy casualties at such engagements as the Battle of the Crater and Chaffin's Farm.