While with the Missouri State Guard, MacDonald served as a captain of artillery and was a staff officer to Sterling Price.

In October, he joined what became the 3rd Missouri Light Battery and was its first commander, fighting at the Battle of Pea Ridge and the Siege of Corinth.

MacDonald was the only militiaman present who would not accept the terms of parole offered, and he was imprisoned in Illinois until ordered released by a judge who ruled that the militia muster had been legal.

[3] As part of the Missouri State Guard, MacDonald fought at the battles of Boonville, Carthage, Wilson's Creek, and Lexington as a captain of artillery[6] and staff officer for Sterling Price.

[9] MacDonald's battery transferred to the Confederate army in January 1862, and the unit saw action in the Battle of Pea Ridge and the Siege of Corinth.

Anxious to retake Missouri for the Confederacy, MacDonald also presented Hindman with far-fetched and unrealistic plans, including one that suggested bringing a force into Kansas in order to leave "the whole Country devastated and laid waste", and then moving into Missouri, where MacDonald believed that 80,000 men could be recruited and armed with pikes.

[12] Other service performed by MacDonald for Hindman included conducting interviews to produce a report on a Confederate defeat at the Battle of Old Fort Wayne.

[13] MacDonald had failed to recruit enough men to form a cavalry regiment, so he found himself commanding John S. Marmaduke's provost guard in November.

[14] Early in the action at Prairie Grove, MacDonald and his men saved Joseph O. Shelby from capture by Federal forces.