On May 17, the 6th Missouri was part of a Confederate force tasked with holding the crossing of the Big Black River. In the ensuing Battle of Big Black River Bridge, the Confederate line was broken, and a rout for the river crossing ensued. The 6th Missouri did not receive clear withdrawal orders, and did not withdraw from the line until the regiment was almost surrounded. After the retreat across the Big Black River, the 6th Missouri entered the defenses of Vicksburg, and took part in the siege of Vicksburg. On May 19, the 6th Missouri Infantry, along with the 1st and 4th Missouri Infantry (Consolidated) and the 5th Missouri Infantry, were used to plug weak points in the Vicksburg defensive perimeter. On May 22, the 6th Missouri strengthened the Confederate line near a point known as the Stockade Redan, helping to repulse Union attacks.