After the American Civil War and garrison duty in the East, the regiment was transferred to the Northern Plains and served in frontier forts.

The regiment's efforts included keeping civilians out of the Black Hills of Dakota Territory that had been ceded to the Lakota Sioux in the Fort Laramie Treaty of 1868.

In 1869, the 22d Infantry was involved in actions at the Oglala Lakota Pine Ridge Indian Reservation, in South Dakota.

In December 1890, and January 1891, the regiment participated in repressing the Ghost Dance on the Sioux Reservation in South Dakota, and in 1891, and 1892 patrolled throughout Montana.

[9] On 18 April 1906, just after the 1906 San Francisco earthquake, recently retired Captain Edward Ord of the 22nd Infantry Regiment was appointed a Special Police Officer by San Francisco Mayor Eugene Schmitz and liaisoned with Major General Adolphus Greely for relief work with the 22nd Infantry and other military units involved in the emergency.

Ord later wrote a long letter[9] to his mother on 20 April regarding Schmitz's "shoot-to-kill" order and some "despicable" behavior of certain soldiers of his former regiment from the Presidio who were looting.

This posting would be one of the last large-scale presence of Army troops since the 1898 gold rush and before the telegraph was replaced with a series of wireless stations.

While not joining in the pursuit of Pancho Villa, they guarded the border region around Douglas, Arizona, and maintained the peace in that area during their time there.

The regiment was the largest organized combat-ready Army presence in New York City during the war where it was engaged in homeland protection duties: guarding tunnels, bridges, rail lines and other important transportation infrastructure that moved troops and material for the war to the city and port.

One battalion was also posted to Washington, D.C. as the primary Army presence in that city, where they also protected vital transportation and military infrastructure.

The regiment assumed command and control of CCC District D, Fourth Corps Area in May 1935 from the 69th Coast Artillery.

[13] The 22nd then moved to Camp Gordon, Georgia on 27 December 1941, where it was reorganized under a "motorized" table of organization and equipment (TO&E) on 9 September 1942.

The regiment continued to train for combat, moving on to Camp Gordon Johnston, Florida on 28 September 1943, and to Fort Jackson, South Carolina on 1 December 1943.

On 14 September its 3d Battalion broke through the Siegfried Line near Buchet, but neither the regiment nor other formations of 4th Division were able to exploit a success because of rough terrain lacking good roads, bad weather hampering air and artillery support and several other causes.

The 22d then moved to Belgium on 28 January 1945, and re-entered Germany on 7 February 1945, where it remained on mop-up and occupation until 12 July 1945, when it returned to the New York POE, and moved to its temporary home at Camp Butner, North Carolina while the regiment trained for movement to Japan; however, the war in the Pacific terminated, and the regiment remained at Camp Butner until it was inactivated on 5 March 1946.

The unit reactivated on 1 June 1940 at Fort McClellan, Alabama, before inactivating on 1 March 1946 at Camp Butner, North Carolina.

It was deployed to South Vietnam as part of the 2d Brigade of the 4th Infantry Division and conducted operations in the Central Highlands.

This included fixed site security, patrols, observation posts, a quick reaction force, and also playing a role in escorting and transporting detainees.

Originally commanded by Lieutenant Colonel Mark Woempner from March through June 2003, the battalion secured Tikrit in northern Iraq.

During this time, the battalion secured their area of operations, engaged in assisting the local population, and fought against the extremist groups.

Once established at Fort Hood, Texas, the battalion immediately began preparations for another Operation Iraqi Freedom deployment.

The battalion returned to Fort Carson, where they served and continued to train, maintaining a state of readiness should the nation require their service anywhere in the world.

The unit reactivated on 1 June 1940 at Fort McClellan, Alabama, and following the end of World War II, inactivated on 1 March 1946 at Camp Butner, North Carolina.

The unit reactivated in September 1976 at Fort Carson and was assigned to Wiesbaden, Germany as part of the 4th Infantry Division (Forward).

The 2nd Battalion also provided infantry soldiers to the UN for a QRF sent in to rescue members of Task Force Ranger who were pinned down during a raid in what is known as today as the Battle of Mogadishu.

The battalion deployed to Operation Iraqi Freedom again in 2007–2008 to Kirkuk as part of the Surge ordered by President George W. Bush.

The "Commanders Emergency Relief Program" (CERP) strategically used money as a means to turn the tide of battle.

SSG Michael Ollis of Co B heroically lost his life during the defense of FOB Ghazni, and was awarded the Distinguished Service Cross, as well as the Polish Gold Medal.

[16] The unit returned home to Fort Drum, NY in June 2016 after handing control over to 2nd Brigade Combat Team, 101st Airborne Division (Air Assault).

They conducted a relief in place of the 2nd Battalion, 505th Infantry Regiment and provided support and additional troops to augment SOJTF-A.