Slaughter resigned from the school on July 6, 1846, because he accepted a commission in the U.S. Army, becoming a 2nd Lieutenant in the newly formed regiment of Voltigeurs and Foot Riflemen, recruited to fight in the Mexican–American War.

Slaughter accepted a commission as first lieutenant, Corps of Artillery in the Confederate States Army but soon became Inspector-General on the staff of General P.G.T.

After the bombardment of Pensacola, in which Lieutenant Slaughter rendered valuable service under fire, General Beauregard reported that probably more than anyone else in his command, he was indebted for the patient labor and unceasing vigil given to the organization and instruction of the troops.

Slaughter continued in that position through the Kentucky Campaign, and was then assigned to the charge of the troops of Mobile, Alabama, that port being threatened by Federal invasion.

During the remainder of the war he played an important part in Confederate affairs in Texas, for some time performing the duties of chief of staff.

[7] Slaughter participated in the last significant land battle of the American Civil War at Palmito Ranch in Texas on May 13, 1865.

"[8] Upon Lee's Surrender at Appomattox Court House, Brigadier General Slaughter fled to Mexico, where he stayed for several years and worked as a Civil Engineer.