The sixth-seeded Eagles (12-19), who have won nine of the last 13 Big South tournament titles, will face No. 7 Virginia Military Institute in the semifinals Thursday night.
Two 3-pointers by Middleton and a jumper by George Valentine—all assisted by Joab Jerome—gave Winthrop a 28-19 lead after the third-seeded Camels (17-15) had scored six straight points.
Campbell never got closer than seven points after that and trailed by double digits all but 1:10 of the second half.
Andre Jones scored 14 points for Winthrop, which lost five of its final regular-season games, including the last three. Jerome finished with nine assists and eight points for the Eagles.
Darren White scored 15 points to pace Campbell, which won both of its regular-season games against Winthrop.