Leake (6-3) rebounded from a loss in his previous outing against St. Louis, yielding only three hits and one walk while striking out six in the 103-pitch effort.
Aroldis Chapman racked up his 17th save as the Reds reeled off a third straight win against the Cubs in their four-game series, which wraps up Thursday.
Brandon Phillips erased a 1-0 deficit with a sixth-inning RBI single and Todd Frazier socked a solo homer in the next frame to supply the winning margin.
The loss was hung on Chicago's Travis Wood (5-5), who gave up four hits and let two runners reach home through seven frames.
Nate Schierholtz lofted a bases-empty homer for the Cubs.