During the war he served as an aide to (then brigadier general) Winfield Scott, and developed a friendship with him. Worth later named his son Winfield Scott Worth. He distinguished himself at the battles of Chippewa and Lundy's Lane during the Niagara campaign. In the latter battle, he was seriously wounded by grapeshot in the thigh. He was not expected to survive, but after a year's confinement he emerged with the breveted rank of Major--though he would remain lame for the rest of his life.
After the war he was Commandant of Cadets at West Point and would rise to the rank of Colonel in 1838 when he was put in command of the newly-created Eighth Infantry Regiment. Using his own tactics he successfully prosecuted the Second Seminole War in Florida and was made a brevet brigadier general in 1842. Eventually, he convinced Secretary of War John C. Spencer to allow the remaining Indians in the territory to confine themselves to the region south of Peace Creek, and declared an official end to the war in August of that year.
He took part in the siege of Veracruz and engaged in the following battles of Cerro Gordo, Contreras and Churubusco. In Mexico City Scott ordered Worth to seize the Mexican works at the Molino del Rey. Worth and Scott's friendship came to a head when Scott refused to allow Worth to modify the attack and the battle caused the 1st Division severe casualties, much to Worth's dismay. Worth later renamed his son Winfield Scott to William. He next led his division against the San Cosme Gate at Mexico City. When U.S. forces entered Mexico City, Worth personally climbed to the roof of the National Palace and took down the Mexican flag replacing it with the Stars and Stripes.
The cities of Fort Worth, Texas and Lake Worth, Texas, the village of Worth, Illinois, Worth County, Georgia and the Lake Worth Lagoon in Florida, and consequently, the city of Lake Worth, Florida on its shores, are named in his honor. Worth was married to a woman named Rebecca C. Goodman.