Bjorn Ruytinx netted the only goal of the game for Leuven 17 minutes from time against a Waasland-Beveren side which had been a man down since the 37th-minute dismissal of Cedric D'Ulivo.
The result was enough to secure top spot in the pool for Leuven - by virtue of goals scored - from Mechelen, which rounded off its campaign with a 2-1 triumph at Charleroi.
In Group A, Gent - already assured of top spot - had to settle for a 1-1 draw at Mons.
Leuven now faces a play-off against Gent to determine which team will go head to head with the side finishing fourth in the Championship play-off for the final Europa League berth.
Also in Group A, Lierse prevailed 3-0 at KV Kortrijk thanks to second-half goals from