San Antonio and the Alamo played a critical role in the Texas Revolution. In December 1835, Ben Milam led Texian and Tejano volunteers against Mexican troops quartered in the city. After five days of house-to-house fighting, they forced General Martín Perfecto de Cós and his soldiers to surrender. The victorious volunteers then occupied the Alamo — already fortified prior to the battle by Cós' men — and strengthened its defenses.

On February 23, 1836, the arrival of General Antonio López de Santa Anna's army outside San Antonio nearly caught them by surprise. Undaunted, the Texians and Tejanos prepared to defend the Alamo together. The defenders held out for 13 days against Santa Anna's army. William B. Travis, the commander of the Alamo sent forth couriers carrying pleas for help to communities in Texas. On the eighth day of the siege, a band of 32 volunteers from Gonzales arrived, bringing the number of defenders to nearly two hundred. Legend holds that with the possibility of additional help fading, Colonel Travis drew a line on the ground and asked any man willing to stay and fight to step over — all except one did. As the defenders saw it, the Alamo was the key to the defense of Texas, and they were ready to give their lives rather than surrender their position to General Santa Anna. Among the Alamo's garrison were Jim Bowie, renowned knife fighter, and David Crockett, famed frontiersman and former congressman from Tennessee.

The final assault came before daybreak on the morning of March 6, 1836, as columns of Mexican soldiers emerged from the predawn darkness and headed for the Alamo's walls. Cannon and small arms fire from inside the Alamo beat back several attacks. Regrouping, the Mexicans scaled the walls and rushed into the compound. Once inside, they turned a captured cannon on the Long Barrack and church, blasting open the barricaded doors. The desperate struggle continued until the defenders were overwhelmed. By sunrise, the battle had ended and Santa Anna entered the Alamo compound to survey the scene of his victory.