The 16th Regiment fought in numerous battles, taking heavy casualties at Antietam and Spotsylvania Court House before surrendering after Union troops broke through the defenses of Petersburg, Virginia, on April 2, 1865.

The regiment was the only Mississippi unit to participate in the valley campaign, and their performance under fire at Port Republic earned them praise from General Richard S.

At the Battle of Gaines' Mill on June 27, the 16th Mississippi alongside the 21st North Carolina charged a fortified Union position, forcing the Federal troops to retreat.

General Isaac R. Trimble praised the regiment in his official report, writing that "the charge of the Sixteenth Mississippi and Twenty-first North Carolina, sustained from the first movement without a falter, could not be surpassed for intrepid bravery and high resolve.

[1][6] The 16th then moved north to participate in the Gettysburg campaign, but was held in reserve until late in the evening of July 2, seeing limited action during the second day of the battle.

This location was the site of some of the fiercest combat of the civil war, as Union and Confederate troops made desperate attacks and counter-attacks over nearly 24 hours of continuous battle.

During the Battle of Globe Tavern, Harris' brigade charged the Union trenches, taking heavy fire and suffering numerous casualties, including Col. E.C.

The 16th Mississippi was among the last defenders of Fort Gregg that day, holding the fortifications against superior numbers to allow the remnants of Robert E. Lee's army to retreat until they were overwhelmed by Union forces.