Leake (8-9) surrendered three runs on nine hits over seven complete innings, notching his third win in four starts. The right-hander walked one and struck out three.
With the score tied in the second inning, the Reds scored three times to put the game away.
Dioner Navarro drew a lead-off walk from Pirates starter Kevin Correia (10-9), went to second on Leake's hit and came home when Brandon Phillips' grounder went off the glove of shortstop Clint Barmes for a double.
Then, with Drew Stubbs at the plate, Correia uncorked a wild pitch. Bucs catcher Michael McKenry chased it down and tried to shovel the ball to Correia covering the plate, but it hit a sliding Leake and bounced away, allowing Phillips to score a second run.
Phillips also homered for the National League Central leading Reds, who clinched their three-game series.
Jonathan Broxton collected his first save of the season.
Correia allowed four runs (three earned) on seven hits over six full innings.
Alex Presley and Gaby Sanchez homered for Pittsburgh.