Chicago won the opener Monday, 12-7.
The hosts snapped their three-game losing streak, while the Cubs had won six of their last eight games.
In his final start of the 2011 season due to an innings limit, Leake (12-9) allowed six hits while walking two and striking out two. Francisco Cordero notched his 33rd save of the year with a 1-2-3 ninth.
Ryan Dempster (10-12) absorbed his fourth straight loss despite throwing a season-high 128 pitches in seven innings. He allowed two runs on six hits and six walks. He struck out eight.
Dempster has not won a start since Aug. 11 against Washington.
Cueto, a 25-year-old who signed as an undrafted free agent in 2004, went to 9-5 on the season with a 2-1 win at Washington on Aug. 17 after allowing a run on six hits with no walks and five strikeouts.
He's gotten no-decisions in each of his four starts since while trying for a third straight season with double-digit victories after debuting with a 9-14 mark as a rookie in 2008.
He won 11 times in 2009 and 12 times last season, but has pitched to a career- best 2.36 earned run average so far this year, nearly a run-and-a-half lower than his career mark of 3.85.
In four outings since defeating the Nationals, he's allowed 13 runs on 28 hits in 24 innings while the Reds have gone 3-1.
The Cubs counter with second-year righty Casey Coleman, who hasn't won since a 5-1 decision in Florida on May 19.
He is 0-4 in nine outings since and has plunged to 2-7 overall after winning four of six decisions as a rookie in 2010.
He pitched five innings and allowed four runs on eight hits in a 5-4 loss to the New York Mets in his last start on Sept. 9.
The Cubs are 0-9 in the last nine games he's pitched.
Coleman has no decisions in three career meetings with the Reds, allowing eight runs on 14 hits in 15 innings.
The Reds lead the season series, 9-7.