In July 1845, the 2nd Dragoons deployed to Texas as part of Brigadier General Zachary Taylor's Army of Observation. On April 25, 1846, a patrol consisting of Companies C and F under the command of Captain Seth Thornton was ambushed by Mexican forces along the northern bank of the Rio Grande. This engagement, known as the Thornton Affair, prompted President James K. Polk to declare that hostilities had commenced, marking the official start of the Mexican-American War.
The regiment served as a key maneuver element in the opening engagements of the conflict, notably at the Battle of Palo Alto on May 8, 1846. During the subsequent Battle of Resaca de la Palma, Captain Charles A. May led a mounted charge that successfully overran and silenced a Mexican artillery battery. This action popularized the command, "Remember your Regiment and follow your officers," which remains a foundational motto within the unit. In November 1847, a small patrol led by Sergeant Jack Miller engaged and defeated a larger Mexican cavalry force near Monclova using mounted saber tactics. The regiment participated in every major campaign of the war, ultimately receiving 14 green and gray campaign streamers for its service.
Throughout the conflict, the regiment played a dual operational role, supporting both General Taylor's northern campaign and Major General Winfield Scott's southern campaign toward Mexico City. The Dragoons provided vital intelligence, route reconnaissance, and line-of-communication security. Elements of the regiment participated in the Siege of Veracruz and the subsequent inland march, frequently operating as the vanguard to locate and probe enemy defensive belts.
Following the capture of Mexico City, the regiment transitioned to occupation duties. They were tasked with countering guerrilla forces, protecting civilian populations, and ensuring the safety of long-distance supply trains operating across hostile territory. The regiment maintained this high-tempo security posture until the ratification of the Treaty of Guadalupe Hidalgo in 1848 effectively ended the war.