After the Louisiana Purchase of 1803 from France doubled the size of the United States, additional territories coveted by America were largely controlled by Spain. Florida was acquired from Spain in 1819. In 1821, Mexico achieved its independence from Spain, so Mexico then held lands sought by Washington. These territories were lightly populated, so Mexico's grip on them was tenuous. Also, Mexico's new government was extremely unstable, and this had an adverse impact on its foreign diplomacy.

Concerned by its lack of control over its northern province of Texas, Mexico encouraged settlement there during the 1820s. The overwhelming majority of the settlers were Americans, though. Washington permitted and encouraged American settlement; the most famous American settlement was led by Stephen Austin. These settlers caused problems, because most of them were non-Catholics and they were slaveholders. Mexico was a Catholic nation, and slavery was forbidden. Also, the settlers were annoyed by Mexican efforts to govern them.

Alarmed by the settlers' recalcitrance, Mexico passed a law in 1830 to stop American settlement of Texas. Tension between the settlers and Mexican authorities increased steadily. Austin tried to negotiate an agreement with the Mexican government, but he failed. In 1835, war broke out between Mexico and Texas. Although the Texans lost at Alamo, they won the war and their independence in 1836. Texas then applied for statehood.

In 1844, James Polk became president, and he wanted to annex Texas, California, and other Mexican territories. He tried to buy them, but Mexico refused. After a skirmish on the Texas border, Polk eagerly led America to war against Mexico in 1846. Mexico was badly beaten, and it had to give up nearly half of its territory when the war ended in 1848.