Edmund Pendleton Gaines was born in Culpeper County, Virginia, on March 20, 1777. At the age of 22, Gaines joined the Sixth United States Infantry in Tennessee, where he had grown up. In 1807, he became captain of the Second United States Infantry. During this tenure, he was involved in the arrest of Aaron Burr, the American vice-president who allegedly killed Alexander Hamilton in a duel.

During 1830-1831, Gaines opposed the use of the militia on account of its recklessness. Instead, he tried to negotiate with the native people; he called a council with Black Hawk and Keokuk. Gaines requested Black Hawk leave Saukenak under the terms of the treaty of 1804. Black Hawk, who questioned the legitimacy of the treaty, refused to co-operate. Gaines then decided to call upon the militia, which made their way to Saukenak. But, Black Hawk and his followers had escaped the night before. The militia, frustrated, began to pillage and burn the town. Gaines had trouble controlling the men. Following this incident, Gaines held another council with the native chiefs. This time Black Hawk reluctantly signed a treaty obliging him to leave Saukenuk for good.

Gaines's military career continued to flourish as he assumed several high-ranking positions, including commander of Military Department One, and commander of the entire eastern United States.

Overstepping the boundaries of his authority, Gaines called upon volunteers during the Mexican War, a decision that would send him to a court of inquiry. Gaines defended himself and all charges were dismissed.

General Edmund Gaines died of cholera on June 6, 1849. At the time, he was married to Kyra Clark Whitney of New York, his third wife.