In July 1838, Congress authorized formation of the Eighth Infantry regiment as part of a general army increase bill. After a brief tour of duty along the nation's northern border, the regiment was transferred to Florida, where it participated in the Second Seminole War. On the eve of the war against Mexico, the Eighth was transferred to Texas with Zachary Taylor's army of occupation. The regiment fought with Taylor as he drove south from Corpus Christi to Monterrey, taking heavy losses but winning recognition for its role in eight engagements against Mexican troops. After the Treaty of Guadalupe Hidalgo, the Eighth Infantry was deployed in Texas and New Mexico against various groups of Apache Indians. Organized into ten companies, it gradually assumed primary responsibility for protecting the trail between San Antonio and Santa Fe during the 1850s. Small detachments of the Eighth, occasionally riding borrowed horses, conducted numerous pursuits against Indians deemed hostile by the federal government, but long-range skirmishing rather than pitched battles usually characterized the decade's fighting. Routine duties in the army's scattered posts west of San Antonio, however, dominated the daily lives of most of the regiment's military personnel. The soldiers particularly detested fatigue and construction duty; desertion, a chronic problem among the antebellum army as a whole, also plagued the Eighth Infantry.
In February 1861, Gen. David E. Twiggs surrendered federal posts in Texas to officials of the state Secession Convention. According to these terms, the garrisons of West Texas posts, including much of the Eight Infantry regiment, were to march to the Texas coast, where they would be allowed safe passage to the North. Although several of the regiment's officers resigned their federal commissions and joined the Confederate Army, almost all of the enlisted personnel remained loyal to the Union. After the scattered garrisons had united and were marching toward San Antonio, news of the firing upon Fort Sumter, South Carolina, led Texas officials to reverse the earlier agreement. Nearly 400 Unionist Eighth Infantrymen under Bvt. Lt. Col. Isaac V. D. Reeve were forced to surrender to a much larger Texas force near San Lucas Springs. The Eighth's remaining officers were paroled the following year, but most of the enlisted personnel remained under guard in Texas until exchanged for Confederate prisoners in February 1863. During the Civil War, elements of the old Eighth Infantry were reconstituted as part of the Fifteenth Infantry, which fought for the Union on the eastern front. Following postwar army reorganization, the Eighth Infantry fought in campaigns against the Indians in Montana (1872) and Arizona (1876, 1886). The regiment participated in the Santiago campaign during the war with Spain (1898), then fought in the Philippine Insurrection. During World War I the regiment was part of the Eighth Infantry Division, and was en route to Europe when the war ended. It served as part of the army of occupation after the armistice. As part of the Fourth Infantry Division, it participated in the Normandy invasion and conquest of Germany during World War II. The regiment later saw combat in Vietnam.