After the Confederate defeat at Port Gibson, the 3rd Missouri Infantry Regiment was engaged at the Battle of Champion Hill, another unsuccessful attempt to stop Major General Ulysses S. Grant's advance against Vicksburg, on May 16. The regiment was routed the next day at the Battle of Big Black River Bridge while serving as part of the rear guard. After Big Black River Bridge, the unit entered the fortifications of Vicksburg, which were soon besieged. During the Siege of Vicksburg, the regiment was often used as a reserve unit, although it saw heavy fighting during a Union assault against the Stockade Redan on May 22. On July 4, the Confederate garrison of Vicksburg surrendered, and the survivors of the regiment were eventually paroled and exchanged. On October 6, the regiment was combined with the 5th Missouri Infantry Regiment to form the 3rd and 5th Missouri Infantry Regiment (Consolidated). The new regiment then fought in the Atlanta campaign in 1864 before being almost annihilated at the Battle of Franklin on November 30, 1864. In early 1865, the consolidated regiment was transferred to Mobile, Alabama, where it surrendered on April 9.