When the Civil War began Rice enlisted on 28 May 1861 in the 39th New York Infantry Regiment quickly becoming a captain of Company B and engaging at the First Battle of Bull Run. Rice was mustered out of the 39th New York Volunteer Infantry Regiment on 12 Sep 1861. The next day Rice became lieutenant colonel of the newly formed 44th New York Volunteer Infantry Regiment (also known as People's Ellsworth Regiment). He fought in the Peninsula Campaign and on July 4, 1862, became the colonel of the regiment. At the Second Battle of Bull Run, Colonel Rice took command of the 3rd Brigade, 1st Division, V Corps when its commander, Daniel Butterfield took command of the consolidated 1st and 2nd Brigades and other ranking officers were wounded on the second day of battle. Rice returned to command of the 44th New York and led it at the battles of Fredericksburg and Chancellorsville. At the Battle of Gettysburg Rice and his regiment were sent to the defense of Little Round Top. During the fighting, brigade commander Colonel Strong Vincent was mortally wounded and Rice once again assumed command of the 3rd Brigade, 1st Division, V Corps and led it for the remainder of the battle. For his service at Gettysburg, Rice was promoted to brigadier general of volunteers on August 17, 1863. In March, 1864 General Rice was in command of the 2nd Brigade, 4th Division, V Corps which he led into action at the Battle of the Wilderness. Rice was mortally wounded at the Battle of Spotsylvania Court House. As he lay dying he muttered the words "turn me over that I may die with my face to the enemy." He died on the Spotsylvania battlefield on May 10, 1864. He was buried at Albany Rural Cemetery, Menands, New York, in section 42, plot 11.