From their humble beginnings in 1767 as a mere 100-man battalion sent to garrison the province of Louisiana (or La Luisiana as the Spanish knew it), recently inherited from the French at the end of the French & Indian War, the unit had expanded to two battalions by the time of Spain's involvement in the American Revolution in the summer of 1779.

Led by Bernardo de Galvez, Spanish Governor of the Provincia de La Luisiana, the unit and several local militias & artillery laid a successful siege to British Fort Richmond in Baton Rouge in September of 1779. In February of 1780 the unit would form part of a multi-unit Spanish Army that would lay another successful siege, this time to British Fort Conde in what is now Mobile, Alabama. In May 1781, a combined army of Spanish peninsular & colonial units and French Army auxilliaries laid siege to the British fort at Pensacola and obtained its surrender. Although the British commander of Pensacola had ordered all British & loyalist units in the Mississippi area to cease fighting, Loyalist James Colbert and an army of 100 Chicasaw Indians and loyalists attacked the Spanish outpost of Arkansas Post in April 1783. Defended by members of the Regiment and the Spanish Royal Artillery, when ammunition dwindled 10 men of the Regiment & 4 Quapaw Indian allies rushed out of the fort to go get help. The attackers, not having seen them exit the fort, feared the Spaniards to be reinforcements & retreated. Thus ending the 2nd westernmost fought battle of the American Revolution and the unit's war record.