In the spring of 1862, Knipe fought in the Valley Campaign against Stonewall Jackson's forces. He was wounded at the First Battle of Winchester. He was again wounded at the Battle of Cedar Mountain. Due to the chain of command changes necessitated during the Battle of Antietam by the death of XII Corps commander Joseph K. Mansfield, Knipe took command of the brigade of Samuel W. Crawford in the first division. Crawford had taken command of the division when Alpheus Williams became acting corps commander.