After John C. Richardson was appointed a Justice of the Supreme Court of Missouri in 1857, Burke went into partnership with Samuel T. Glover (considered the dean of the St. Louis Bar).

In the midst of the violence and tension of the Missouri secession crisis, Burke married 27-year-old Catherine Mackay, daughter of a wealthy surveyor with connections to socially prominent French members of the St. Louis elite.

[6] Burke participated in General Lyon's campaign in pursuit of Maj. Gen. Sterling Price's Missouri State Guard, fighting in the Battle of Dug Spring on August 2, 1861.

[citation needed] On October 3–4, 1862 Burke personally led the Western Sharpshooters in two days of bitter skirmishes during the Second Battle of Corinth.

After the battle Maj. Gen. William S. Rosecrans appointed Burke as Commandant of Corinth, responsible for securing the town, Confederate prisoners, stragglers, and dealing with the large numbers of casualties from both armies.

As usual, the 66th Illinois was used as scout-skirmishers, but were employed as shock troops due to the regiment's high morale and the volume of fire they could generate with their newly purchased sixteen-shot Henry Repeating Rifles.

[citation needed] On May 9, on Maj. Gen. Sherman's orders, McPherson's XVI Corps attacked through Snake Creek Gap in an attempt to cut Confederate Gen. Joseph E. Johnston's railroad supply line at Resaca, Georgia.

The unexpected attack through the Gap succeeded, and the regiment advanced on Col. Burke's orders, single-handedly capturing the lightly held heights above Resaca.

[15] Maj. Gen. James B. McPherson, concerned that his exposed troops might be cut off, ordered his forces which included Burke's advanced brigade, back to Snake Creek Gap.

McPherson ordered Brigadier General Thomas Sweeny's division to move south, and forced a crossing of the Oostanaula River at Lay's Ferry.

[17] When Johnston learned that Sweeny was across the Oostanaula, and in position to threaten the Confederate line of communication, he ordered his forces to evacuate Rasaca, and retreat south.

XVI Corps commander Maj. Gen. Grenville M. Dodge ordered Sweeny to push forward in an attempt to strike at Johnston's army as it retreated.