In the spring and early summer of 1863, "Tuscumbia" performed valuable service during amphibious operations against Vicksburg, Mississippi. On 1 April, she carried Admiral David D. Porter and Generals Ulysses S. Grant and William Tecumseh Sherman on a reconnaissance expedition up the Yazoo River to determine the practicality of landing a force above Vicksburg at Hayne's Bluff. "Tuscumbia" withdrew under heavy fire from shore batteries, prompting the decision to shift operations below Vicksburg to Grand Gulf. "Tuscumbia" participated in the run past the Vicksburg batteries to New Carthage on the night of 16 April and 17 April 1863, towing the damaged transport "Forest Queen" to safety. On 20 April, USS General Price and "Tuscumbia" reconnoitered the Mississippi from New Carthage to Grand Gulf and took part in the attack on the Confederate works at Grand Gulf on 29 April. During the attack, "Tuscumbia" suffered five casualties and was put out of action after taking 81 hits.