[3] During the Civil War, Pettus's son John joined one of the Mississippi regiments in Virginia and was killed at the Battle of Ball's Bluff in October, 1861.

[7] His only recorded act during these 120 hours was to order a special session in Noxubee County to fill the office of a deceased state representative, Francis Irby.

[5] As a state senator, Pettus developed a reputation as a "disunion man of the most unmitigated order", advocating for Mississippi delegates to attend the Nashville Convention and discuss the possibility of secession during the 1850 political crisis.

In his inaugural address, he said that the South's only way to maintain slavery was secession and a Southern Confederacy, and he pledged to defend the "superiority and supremacy of the white race" against "Black Republicans".

While large numbers of volunteers began organizing themselves into military companies immediately after the 1860 Presidential election,[12] Mississippi lacked the funds and arms to supply them.

[14] Some of the Mississippi volunteer regiments were sent to Virginia to join the Confederate Army, while others remained in the service of the state and were sent to the Gulf Coast during the Pensacola campaign to besiege Federal forts and resist any attempt at a coastal invasion.

[15] Ship Island remained under Union control for the rest of the war, serving as a base for the capture of New Orleans and raids on the Mississippi coast.

[17] Despite some discontent that he had mismanaged the military situation and had been too slow to act at the outbreak of hostilities, Pettus was renominated by his party and re-elected as Governor by an overwhelming margin in October 1861.

Pettus, like many other southern governors, sought to keep a state military force under his personal control for home defense, while faced with a War Department seeking to enlist as many men as possible into the Confederate Army.

[19][20] Rates of desertion, absence without leave, and requests for medical discharge from the State Troops were high and they never served as an effective military force.

[22] After the Federal Navy enacted a blockade of the Confederacy, Mississippi's cotton crop could not be exported and exchanged for hard currency and essential goods.

[24] 1862 witnessed battles at Corinth and Iuka in North Mississippi as Union forces sought to capture vital railroad junctions in the state.

Aware that the Mississippi River was a strategic objective for the Union, Pettus encouraged the legislature to allow the impressment of slaves to build defensive works at Vicksburg, Jackson, and Port Hudson, Louisiana.

[26] Ineligible under the Mississippi Constitution to run for a third term, Pettus left office in November 1863 and became a colonel in the State Troops, assigned to recruiting duties at Grenada and Macon.