Garko hit a three-run homer and Sizemore had four hits including a two-run shot as Cleveland improved baseball's best home record to 15-3. The Indians have won eight in a row at Jacobs Field, outscoring opponents 64-28 during the streak.
Cincinnati's Brandon Phillips extended his career-best hitting streak to 20 games with a fourth-inning double, but the Reds lost for the eighth time in their past nine road games.
Lee (2-0) allowed two earned runs and six hits over six innings to improve to 8-0 in 11 career starts against NL opponents. The left-hander is 3-0 against the Reds and the Indians hold a 27-19 advantage over their intrastate rivals in 10 years of interleague play.
Garko hit his sixth homer in a six-run second inning against Kyle Lohse (1-5) and reliever Victor Santos to take a 7-4 lead. Jhonny Peralta had a double and RBI single in the inning, which also included an RBI single by Sizemore and sacrifice fly by Casey Blake.
Sizemore's seventh homer with one out and Garko on base after a single made it 9-4 in the third.
Sizemore went 4-for-5 and has hit .555 (10-for-18) in his past four games to raise his average 37 points to .276. Cleveland's leadoff hitter singled, went to third on a single to right by Blake and scored on a groundout by Travis Hafner in the first to put Cleveland ahead 1-0.
The Reds came back with a four-run second.
Lee hit Adam Dunn with a pitch to start the rally. With two on, first baseman Garko fielded a bunt and threw wildly trying to get Dunn at third. The error loaded the bases. One out later, Ryan Freel tripled to right-center for a 3-1 lead. Freel scored on a sacrifice fly by Phillips.
Lohse lost his fifth straight start. The right-hander, winless in six starts since beating the Chicago Cubs on April 15, allowed seven hits and five earned runs over 1 1/3 innings -- his shortest start since coming up to the majors in 2001 with Minnesota.
Lohse has an 8.03 ERA during his losing streak and fell to 2-7 with an 8.08 ERA in nine career starts at Jacobs Field.
Indians RHP Roberto Hernandez struck out the side on 10 pitches in the seventh. ... Indians RF Trot Nixon played in his 100th consecutive errorless game. ... Sizemore had one stolen base and is 15-for-15 in steal attempts this season. ... Cleveland is 23-5 when scoring four or more runs. ... The Reds have been outscored 39-17 over their past seven games.