In 1861, Morrison helped organize and was appointed colonel of the 49th Illinois Volunteer Infantry Regiment during the Civil War. Shortly after it was as mustered into service on December 31, 1861, the regiment was attached to Ulysses S. Grant's army at Cairo, Illinois. The 49th was formed into a brigade with 17th Illinois and two artillery batteries and, being the senior colonel, Morrison was placed in command of the brigade. Morrison's brigade was designated the 3rd Brigade, 1st Division, District of Cairo and joined Grant's expedition to Fort Henry. Morrison also participated in the Battle of Fort Donelson where his division commander, John A. McClernand, decided to seize a Confederate battery early in the engagement. McClernand selected Morrison's two regiments to lead the attack and decided to attach a third regiment from W.H.L. Wallace's brigade under Colonel Isham N. Haynie as support. However, Haynie outranked Morrison and decided to take command. Despite being the brigade's commander, Morrison willingly obliged to let Haynie lead the attack once it started. To that, Haynie replied, "Colonel, lets take it together." Shortly after the shooting started Morrison was struck in the hip, knocking him off his horse and settling the issue of command. Morrison never returned to the field and resigned his commission on December 13, 1863.