Kawakami (4-6) allowed two hits and two runs in six innings in his first start against Boston since signing a $23 million, three-year contract in January after 11 seasons in Japan.
Matsuzaka (1-5) cost the Red Sox a lot more $103 million over six years, including a $51 million fee for the right to negotiate with him but failed to reach the sixth inning for the sixth time in his last eight starts in his third year with the team.
Garret Anderson went 3 for 3 with four RBIs as the Braves finally gave Kawakami support with seven runs while he was in the game. They had scored just 24 in his other 69 1-3 innings.
Jason Bay got both of Boston's hits, a double and homer off Kawakami, before three relievers pitched three hitless innings.
Atlanta won its second straight game since breaking a four-game losing streak with a 7-0 win at Cincinnati in which McLouth had two hits, a homer and four RBIs.
Boston still has the AL's best home record at 23-10 but kept struggling at the plate after managing just one hit, a homer by Kevin Youkilis, in a 2-1 loss to Florida on Thursday night that ended in the top of the sixth because of rain.
The Braves came out swinging against Matsuzaka, who usually runs up high pitch counts, and had three hits on the first four pitches the total amount of hits that the Red Sox had Thursday and Friday.
After McLouth's 12th homer this season and third in 14 games since being traded by Pittsburgh, Atlanta loaded the bases on a single by Yunel Escobar, a double by Chipper Jones and a walk to Brian McCann. Anderson's walk made it 2-0, but Matsuzaka escaped with a strikeout and double play, extending his streak to 17 straight hitless at bats with the bases loaded.
The Braves added two runs in the fourth on McLouth's RBI double and Escobar's run-scoring single. They made it 6-0 in the fifth on consecutive doubles by McCann and Anderson that drove Matsuzaka from the game, and a sacrifice fly by Casey Kotchman off Justin Masterson.
The Red Sox finally scored in the sixth with two outs on Bay's 18th homer, a two-run shot that gave him an AL best 65 RBIs.
Anderson drove in the last two runs with a single in the seventh and a sacrifice fly in the ninth.