The vessel destroyed Confederate shipping used to ferry troops across the river and enfiladed Southern entrenchments situated behind the fort.

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.

During the attack on the 22nd, Benton, Mound City, Carondelet, and Tuscumbia silenced three water batteries and destroyed four guns.