Cooke's career grew during the Civil War. Made a Brigadier General November of 1861, he was initially assigned with the cavalry elements defending Washington D.C. He first experience in the Civil War was to be in reserve during the Peninsula Campaign in Virginia (March-July 1862), participating in the battles of Yorktown and Williamsburg. As Union forces were repulsed back to the sea, in what became the Seven Days battle toward the end of the Peninsula Campaign, Cooke saw action in the battle of Gaine's Mill and White Oak Swamp. However at Gaine's Mill he was led to more or less sacrifice an entire regiment of regular infantry to delay the Confederate advances. His battle command ended there, by choice, but also by the embarrassment of having his son-in-law, Stuart, beating the U.S. cavalry units attached the Army of the Potomac. Cooke was transferred to Union-occupied Baton Rouge in Louisiana, where he was in charge of recruitment and court-martial boards. He stayed there until the end of the war and in 1866 was made Major General.
From 1866 to 1873, he was in charge of different military departments: Department of the Platte (containing all of Iowa, Nebraska, Wyoming and Utah and portions of Idaho), Department of the Cumberland (essentially areas of Tennessee, Ohio, Kentucky and Georgia) and the Department of the Lakes (containing portions of Wisconsin and Minnesota). Cooke officially retired as a Brigadier General in 1873, after 50 years of service. He retired to Detroit, Michigan and died there in 1895 and was buried in the historic Elmwood Cemetery.
Modern day Vandenberg Air Force Base, in Santa Barbara county, CA, stands on land that was originally occupied army camp, Camp Cooke, named in Cooke's honor.
His friendship and charity with the LDS church and leadership over the Mormon Battalion still resonates with the LDS church today. Historians theorize, but have yet to confirm that the city of St. George, Utah, founded in 1861, was named in General Cooke's honor, my taking his middle name.