While back in Louisiana, Mouton was made interim commander of the District of West Louisiana, part of the Trans-Mississippi Department, and did what he could with the limited men and supplies that he had to fight off Federal attempts to move into the state. His army, attempting to protect the sugar cane farms along Bayou Lafourche, was brushed aside by the U.S. Volunteers under Brigadier General Godfrey Weitzel in the Battle of Georgia Landing at Labadieville, Louisiana, in October 1862, which led to Weitzel destroying much of the crops in that area. With the arrival of Confederate Major General Richard Taylor, Mouton was made a brigade commander and given the rank of brigadier general. The duo of Mouton and Taylor would prove to be one of the most efficient during the war and they, along with cavalry commander Thomas Green, would harass, confuse, frustrate, and delay Union attempts to secure the Bayou Teche region of southern Louisiana. Mouton's leadership in his Louisiana brigade helped the Confederates undermine Union attempts to access the rich Bayou Teche region. He was a key participant in the battles of Irish Bend, Fort Bisland, Franklin, and Bayou Borbeau, along with numerous other smaller skirmishes.