William H. Powell was the last artist to be commissioned by the Congress for a painting in the Rotunda. His dramatic and brilliantly colored canvas shows Spanish conqueror and explorer Hernando DeSoto, riding a white horse, the first European to view the Mississippi River, in 1541. As De Soto and his troops approach, the Native Americans in front of their tepees watch, and a chief holds out a peace pipe. In the foreground is a jumble of weapons and soldiers, suggesting the attack they had suffered shortly before. To the right, a monk prays as a crucifix is set in the ground.

Powell (1823–1879) was born in New York and raised in Ohio. He studied art in Italy and worked on the painting in Paris. He also painted The Battle of Lake Erie, which hangs in the east Senate Grand Staircase in the Capitol.