At the beginning of the Civil War, McLean organized the 75th Ohio Infantry Regiment under authority from Maj. Gen. John C. Frémont and became its colonel September 18, 1861.

When the 75th Ohio was within 10 miles of Staunton, Milroy ordered the march to turn back at Buffalo Gap, so he could engage Jackson.

Milroy made his headquarters at McDowell, Virginia, and Jackson positioned his men east of the town on top of a hill known as Bull Pasture Mountain.

Trying to catch the Confederates by surprise, the Union attacked late on May 8, 1862, in the Battle of McDowell, with McLean leading several regiments up the hill on their right flank.

At the Battle of Cross Keys, McLean was promoted to the command of a brigade, consisting of four Ohio regiments, though he was held in reserve along the Keezletown Road on "Frémont's Final Line."

At the Second Battle of Bull Run, McLean's brigade was placed at the extreme left of the Union line on Chinn Ridge.

McLean's troops took many casualties, but they were able to hold off the Confederates for a half-hour, which allowed Pope to establish a second line of defense further north of Chinn Ridge.

As part of the XI Corps, the brigade stayed posted in Washington during the Battle of Antietam in September, and they were not called on to move again until December.

Since March 10, McLean had grown popular with the men as commander of the First Division of the XI Corps, but Howard opted to replace him with Brig.

McLean was at corps headquarters with Devens when the attack happened (Howard had left the area, inexplicably escorting reinforcements to another part of the battlefield).

Devens refused, possibly because he had been using brandy to dull the pain of a leg injury that occurred the previous day, when his horse ran him into a tree.

McLean commanded a brigade in the XXIII Corps during the Atlanta Campaign and again came into conflict with Howard for alleged failures at the Battle of Pickett's Mill.

The corps took Fort Fisher, and intended to meet the rest of Sherman's army in central North Carolina, but they got as far as Goldsboro before the Battle of Bentonville in March.

Seeing the end of the war coming, McLean resigned his commission April 20, 1865, six days before the surrender of General Joseph Johnston at Bennett Place in Durham, North Carolina.