The regiment fought in the Battle of Mindanao. On 17 April, it conducted an amphibious assault on Mindanao's south-central coast. The 3rd Battalion landed at Malabang and linked up with Filipino soldiers under the Philippine Commonwealth Army, Philippine Constabulary and recognized guerrillas there who had captured the Malabang Airfield. The remainder of the regiment landed at Baras, thirty miles southeast. The regiment embarked on landing craft of the 533d Engineer Boat and Shore Regiment and was transported to Kabacan using the Mindanao River. There, it became X Corps reserve. The arrival of the 162nd RCT allowed the 21st to return to divisional control.