Several months previously, Texians had driven all Mexican troops out of Mexican Texas. Approximately 100 Texians were then garrisoned at the Alamo. The Texian force grew slightly with the arrival of reinforcements led by eventual Alamo co-commanders James Bowie and William B. Travis. On February 23, approximately 1,500 Mexican troops marched into San Antonio de Béxar which is now named San Antonio as the first step in a campaign to re-take Texas. For the next 12 days the two armies engaged in several skirmishes with minimal casualties. Aware that his garrison could not withstand an attack by such a large force, Travis wrote multiple letters pleading for more men and supplies, but fewer than 100 reinforcements arrived.

In the early morning hours of March 6, the Mexican Army advanced on the Alamo. After repulsing two attacks, Texians were unable to fend off a third attack. As Mexican soldiers scaled the walls, most of the Texian soldiers withdrew into interior buildings. Defenders unable to reach these points were slain by the Mexican cavalry as they attempted to escape. Between five and seven Texians may have surrendered; if so, they were quickly executed. Most eyewitness accounts reported between 182 and 257 Texians dead, while most historians of the Alamo agree that 400–600 Mexicans were killed or wounded. Several noncombatants were sent to Gonzales to spread word of the Texian defeat. The news sparked a panic and the Texian army, most settlers, and the new Republic of Texas government fled from the advancing Mexican Army.

Within Mexico, the battle has often been overshadowed by events from the Mexican–American War of 1846–48. In 19th-century Texas, the Alamo complex gradually became known as a battle site rather than a former mission. The Texas Legislature purchased the land and buildings in the early part of the 20th century and designated the Alamo chapel as an official Texas State Shrine. The Alamo is now "the most popular tourist site in Texas". The Alamo has been the subject of numerous non-fiction works beginning in 1843. Most Americans, however, are more familiar with the myths spread by many of the movie and television adaptations, including the 1950s Disney miniseries Davy Crockett and John Wayne's 1960 film The Alamo.

Under President Antonio López de Santa Anna, the Mexican government began to shift away from a federalist model. The increasingly dictatorial policies, including the revocation of the Constitution of 1824 in early 1835, incited many federalists to revolt. The Mexican border region of Texas was largely populated by immigrants from the United States. These were accustomed to a federalist government and to extensive individual rights, and they were quite vocal in their displeasure at Mexico's shift towards centralism. Already leery of previous American attempts to purchase Texas, Mexican authorities blamed much of the Texian unrest on American immigrants, most of whom had made little effort to adapt to the Mexican culture.

In October, Texians engaged Mexican troops in the first official battle of the Texas Revolution. Determined to quash the rebellion, Santa Anna began assembling a large force, the Army of Operations in Texas, to restore order. Most of his soldiers were raw recruits, and a large number had been forcibly conscripted.

The Texians systematically defeated the Mexican troops already stationed in Texas. The last group of Mexican soldiers in the region—commanded by Santa Anna's brother-in-law, General Martín Perfecto de Cos—surrendered on December 9 following the siege of Béxar. By this point, the Texian Army was dominated by very recent arrivals to the region, primarily adventurers from the United States. Many Texas settlers, unprepared for a long campaign, had returned home. Angered by what he perceived to be American interference in Mexican affairs, Santa Anna spearheaded a resolution classifying foreigners found fighting in Texas as pirates. The resolution effectively banned the taking of prisoners of war: in this period of time, captured pirates were executed immediately. Santa Anna reiterated this message in a strongly worded letter to United States President Andrew Jackson. This letter was not widely distributed, and it is unlikely that most of the American recruits serving in the Texian Army were aware that there would be no prisoners of war.

When Mexican troops departed San Antonio de Béxar (now San Antonio, Texas) Texian soldiers established a garrison at the Alamo Mission, a former Spanish religious outpost which had been converted to a makeshift fort. Described by Santa Anna as an "irregular fortification hardly worthy of the name", the Alamo had been designed to withstand an attack by native tribes, not an artillery-equipped army. The complex sprawled across 3 acres (1.2 ha), providing almost 1,320 feet (400 m) of perimeter to defend. An interior plaza was bordered on the east by the chapel and to the south by a one-story building known as the Low Barracks. A wooden palisade stretched between these two buildings. The two-story Long Barracks extended north from the chapel. At the northern corner of the east wall stood a cattle pen and horse corral. The walls surrounding the complex were at least 2.75 feet (0.84 m) thick and ranged from 9–12 ft (2.7–3.7 m) high.[Note 1]

To compensate for the lack of firing ports, Texian engineer Green B. Jameson constructed catwalks to allow defenders to fire over the walls; this method, however, left the rifleman's upper body exposed. Mexican forces had left behind 19 cannons, including an 18-pounder, which Jameson installed along the walls. He boasted to Texian Army commander Sam Houston that the Texians could "whip 10 to 1 with our artillery".

The Texian garrison was woefully under-manned and under-provisioned, with fewer than 100 soldiers remaining by January 6, 1836. Colonel James C. Neill, the acting Alamo commander, wrote to the provisional government: "If there has ever been a dollar here I have no knowledge of it". Neill requested additional troops and supplies, stressing that the garrison was likely unable to withstand a siege lasting longer than four days. The Texian government was in turmoil and unable to provide much assistance.[Note 2] Four different men claimed to have been given command over the entire army;[Note 3] on January 14, Neill approached one of them, Sam Houston, for assistance in gathering supplies, clothing, and ammunition.

Houston could not spare the number of men necessary to mount a successful defense. Instead, he sent Colonel James Bowie with 30 men to remove the artillery from the Alamo and destroy the complex.[Note 4] Bowie was unable to transport the artillery since the Alamo garrison lacked the necessary draft animals. Neill soon persuaded Bowie that the location held strategic importance. In a letter to Governor Henry Smith, Bowie argued that "the salvation of Texas depends in great measure on keeping Bexar out of the hands of the enemy. It serves as the frontier picquet guard, and if it were in the possession of Santa Anna, there is no stronghold from which to repel him in his march toward the Sabine."[Note 5] The letter to Smith ended, "Colonel Neill and myself have come to the solemn resolution that we will rather die in these ditches than give it up to the enemy." Bowie also wrote to the provisional government, asking for "men, money, rifles, and cannon powder". Few reinforcements were authorized; cavalry officer William B. Travis arrived in Bexar with 30 men on February 3. Five days later, a small group of volunteers, including Davy Crockett, arrived.