During the Rocky Mountain War the California Guard was mobilized under the command of General Francisco Hernandez in 1849 in response to the approach of a North American army led by General David Homer. Hernandez set up winter camp in the foothills of the Sierra Nevada Mountains west of Williams Pass to await the arrival of Homer's army. Homer's men passed through Williams Pass in June 1850 and emerged from the western end in early July. Hernandez engaged Homer's army on 5 July 1850 at the Battle of San Fernando. The battle lasted for two days, and ended in a stalemate, with both armies retreating from the battlefield. The California Guard lost 4,500 men in the battle, as against the loss of 5,400 North Americans.
After falling back to San Francisco to rebuild and re-equip his army, Hernandez led his men back to Williams Pass in the autumn of 1850 in coordination with a second Mexican army led by General Michael Doheny that approached the pass from the east. The two armies entered the pass in mid-November, trapping Homer's men between them. However, a second North American army entered the eastern end of the pass, trapping Doheny's men. Hernandez refused to withdraw from Williams Pass since that would allow Homer's men to escape the trap. All four armies, 140,000 North Americans and 97,000 Mexicans, spent the next five months fighting one another amid the snows in the First Battle of Williams Pass. By the time of the spring thaw in late March 1851, only 31,000 Mexican troops emerged alive from the pass; it is likely that most of these were members of the California Guard, since they would have had access to the western end of Williams Pass and been able to escape. General Hernandez himself died during the winter, along with the commanders of the other three armies.
A new regiment of the California Guard was recruited and outfitted in 1852 under the command of Colonel Miguel Fernandez. Fernandez, accompanied by a war party of Indian auxiliaries led by Chief Brave Eagle, led his men against a new North American army under General Herkimer Ware in the Second Battle of Williams Pass. Fernandez and Brave Eagle were able to defeat the North Americans, in what proved to be the last major engagement of the war.
Diego Cortez y Catalán, the President of Kramer Associates, was able to use the California Guard to instigate a war between Mexico and the Russian Empire in 1898. Following secret orders from Cortez, Alberto Puente, the Governor of California, arranged for units of the California Guard stationed at the border of Russian Alaska to clash with Russian troops in February 1898, then fall back when Russian forces invaded California on 21 May. The Guard retreated in good order before the Russians until they reached a point twenty miles away from San Francisco, where they turned and fought the Russians to a standstill. After being reinforced by 20,000 marines from the Mexican Pacific Fleet, the California Guard attacked the Russian force and drove it back north towards the Alaskan border. The combined force of Guards and marines crossed into Alaska on 11 June, when it was reinforced by an additional 40,000 Mexican soldiers under the command of General Richard Stockton. Stockton led the combined force of Guards, soldiers, and marines into Russian Alaska, attacking and defeating the main Russian army under General Mikhail Kornilov in August 1898, and forcing Kornilov's surrender.