By early 1865, Mobile was the only significant Gulf port still in Confederate hands. Admiral David Farragut's fleet had won the Battle of Mobile Bay the previous August, famously damning the torpedoes on its way through the harbor defenses. But controlling the bay was not the same as controlling the city. Mobile sat at the head of the bay, protected on its eastern flank by a chain of fortifications stretching across Baldwin County. Spanish Fort anchored those defenses: Fort Huger, Fort Tracey, Fort McDermott, Fort Alexis, Red Fort, and Old Spanish Fort formed an interconnected line of earthworks and batteries. As long as Spanish Fort held, Union forces could not approach Mobile from the east.

General Canby assembled a massive force for the campaign. His XIII and XVI Corps crossed the Fish River at Marlow Ferry and advanced north along the eastern shore of Mobile Bay, pushing Confederate skirmishers back into their prepared defenses. A second column of around 13,000 men moved north from Pensacola. On March 27, 1865, Canby's forces converged at Danley's Ferry and immediately began siege operations against Spanish Fort. The terrain favored the defenders: marshes and waterways channeled the Union approach, and the Confederate earthworks provided strong firing positions. Canby's men began digging their own siege lines, inching closer day by day.

What followed was a grinding siege rather than a dramatic assault. Union forces gradually enveloped Spanish Fort, completing the encirclement by April 1. Confederate defenders fought from their entrenchments, knowing that every day they held was another day Mobile remained in Southern hands. The six Louisiana infantry regiments and five Alabama infantry regiments under Gibson's command were outnumbered beyond any reasonable hope of victory, but they held their ground through constant shelling and probing attacks. Estimated casualties from the siege totaled 657 Union and 744 Confederate soldiers. On the night of April 8, with the position finally untenable, Gibson ordered an evacuation. Most of his force escaped across the bay to Mobile under cover of darkness.

Spanish Fort's fall triggered a rapid chain of events. Five miles to the north, Fort Blakeley was already under pressure; Union troops had begun shifting northward as early as April 1, when Spanish Fort's fate became clear. Fort Blakeley fell on April 9, the same day Lee surrendered at Appomattox. With both forts gone, Mobile's eastern defenses collapsed. The Confederate Army of Mobile evacuated the city, and Union troops entered Mobile unopposed on April 12, 1865. The last major Gulf port had finally changed hands. Today the earthworks at Spanish Fort are preserved as a historic site in Baldwin County, the trenches and battery positions still visible in the landscape as reminders of those twelve days when the outcome of the war had already been decided everywhere except along the shores of Mobile Bay.