The 1st Dragoons were sent in October of 1833 to be nearby to Fort Gibson in the Arkansas Territory, and wintered there until June of 1834, when they were sent to take part in the Pawnee Expedition. After that, the main headquarters of the 1st Dragoons was established at Fort Leavenworth, Kansas, while the individual companies were disbursed to various frontier postings in Texas and the Missouri territory.

With the outbreak of hostilities between the US and Mexico, the majority of the 1st Dragoons were sent as part of a detachment to the far western end of the border, particularly to Sante Fe, and then on to Southern California. There they were instrumental in the defeat of Mexican garrisons including the Battles of San Pasqual, Rio San Gabriel, and La Mesa, the final of which allowed them and the rest of the US forces to capture the city of Los Angeles. Other companies took part in the Battle of Cañada during the Taos Revolt of local Mexicans and Mexican-aligned Pueblo Indians, and Company F were the main escort of General Winfield Scott on his route from Veracruz to Mexico City, and took part in the siege there. 

Not all of the 1st Dragoon's history could be labelled "illustrious," as during the inter-war years they continued their earlier frontier-guarding missions, and in particular helped guard the route of the Oregon Trail. One of the most infamous actions was the 1850 "Bloody Island" Massacre, where a group of Pomo Indians running from captivity and brutal enslavement by the Kelsey brothers were hunted by the 1st US under the command of Lieutenants J.W. Davidson and Nathaniel Lyon. The troopers were under the specific orders by superiors to exterminate the Indian band, and they happened upon a group of Pomo women, children, and elderly on what was considered a safe island on Clear Lake. The troopers murdered everyone they could see, while many tried to run or hide, they were systematically hunted and killed. One of the very few survivors was six-year old Ni'ka, also named Lucy Moore, who survived by staying under a bank and underwater while breathing through a tule reed.  

Companies C and E also took part in the Rogue Indian War in southern Oregon Territory, while in 1855 the headquarters was moved from Kansas to Fort Tejon, California at the same time as additional cavalry units - the pre-war 1st and 2nd US Cavalry - were also formed by Congressional act. The 1st Dragoons remained a largely dispersed group fighting engagements or guarding frontier areas from the Southwest to Northern Oregon. 

In May of 1861, with the outbreak of the Civil War, the 1st Dragoons were redesignated the 1st US Cavalry whereas the 1855 1st US Cavalry were redesignated the 4th Cavalry. Two companies remained in New Mexico Territory, but the vast majority of the command was transferred by steamship from California, on foot across the Panama isthmus, and then by ship again to Washington D.C., not arriving until the end of January, 1862. While the New Mexico garrison was not left out of the fight due to Confederate contingents operating there, those sent eastward were attached to the Army of the Potomac's 2nd Brigade of the Cavalry Reserve, and were first engaged during the Peninsula Campaign later in 1862. 

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In 1863, the troopers continued to be engaged in fights like Beverly Ford, Upperville, and Gettysburg, while in June of that year those remaining in New Mexico were temporarily dissolved, the men transferred to Carlisle Barracks in Pennsylvania, and then reformed in new companies to join their compatriots in Maryland by October.

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By 1864, the newly=whole regiment was heavily engaged as both pickets along the Rapidan River and as a cohesive unit fighting in several battles and counter-raids such as that undertaken by General Custer against Charlottesville, Virginia. They were also heavily involved in actions while under the command of General Sheridan in actions such as Spotsylvania Courthouse, the raid around Richmond, Beaver Dam Station, Yellow Tavern, Old Church, and Cold Harbor. They were also quickly redeployed by ship again to Washington D.C. to help repel the brief siege of the capital by General Early.

Finally, in 1865, the regiment followed Sheridan on his destruction of the Shenandoah Valley's rail and canal infrastructure, as well as the Battle of Waynesboro which captured the remnants of Early's army. They continued to target more Confederate supply depots and canalworks to hamper their logistic support. In March they supported the battles of White Oak Road, Dinwiddie Courthouse, and Five Forks which saw them charge an entrenched rebel position and carry the day with two-hundred prisoners in tow. Following the battle and surrender of Lee's forces at Appomattox Courthouse, they were on the way to North Carolina to meet up with General Sherman's forces before news reached them of Johnston's surrender. At that point they took part in the Grand Review in Washington D.C. prior to going back to further frontier work in the post-war years.