The regiment left Camp Franklin in Dubuque, Iowa, on September 16, 1862, on board the sidewheel steamer Henry Clay and two barges tied alongside.

The battle ended with Confederates withdrawing to the south and Federal soldiers to Lebanon before returning to Houston.

The brigade saw action in Mississippi at Port Gibson, Black River Bridge and the Siege of Vicksburg.

On May 17, 1863, the 21st and 23d regiments led an assault on entrenched Confederates at the Big Black River bridge, charging out of a meander to the enemy's left flank causing the Rebel defenses at the Black River bridge to collapse and forcing them to retreat.

The regiment then took part in expeditions in Louisiana and then moved to the south coast of Texas at Matagorda Island, Indianola and other nearby locations.