Ampudia began his career in the Spanish army, and emigrated to Mexico following the Mexican War of Independence. In 1836, Ampudia served with the Mexican artillery at the Siege of the Alamo and later saw heavy combat at the Battle of San Jacinto. During border skirmishes with Texas in the early 1840s, Ampudia was never defeated, and earned the grudging respect of his enemies across the border.
Briefly appointed as commander-in-chief of the Mexican Army of the North in 1846, Ampudia was removed from command following the brutal public execution of a local guerrilla leader on his personal orders. As a conservador (a member of Mexico's conservative faction), Ampudia was quickly relegated to a staff position in favor of his liberal rival, General Mariano Arista. At the Battle of Palo Alto, Ampudia harshly criticized Arista for what he saw as "unacceptable tactical blunders" and continued his criticism at the Battle of Resaca de la Palma – a defeat for which Arista partially blamed him.
During the long retreat south, Ampudia was appointed commander-in-chief of the Army of the North, in time to command Mexican forces at the Battle of Monterrey. Despite orders from Antonio López de Santa Anna that he was to retreat to Saltillo, Ampudia chose to stand at Monterrey instead and informed Santa Anna that:
Despite his controversial retreat at Monterrey, Ampudia remained popular in Mexican folklore as "the only man who could defeat Taylor". After the war, Ampudia's policies became gradually more liberal, so that he supported the government of Benito Juárez during the Maximillian Intervention and served with considerable bravery and skill as commander of the liberal Army of the East, in whose command he was gravely wounded. In 1868, Ampudia died (possibly from complications arising from his wartime injuries) and was buried in the Panteón de San Fernando.
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