Kearns drove in four runs with two homers against his former team as the Indians beat the Washington Nationals 7-2 on Friday night.
"Austin is the ultimate pro and it's good to see him healthy," Indians manager Manny Acta said.
Travis Hafner also homered to help give Acta a win in his first game against the team that fired him last July 13. That was only a month after Washington drafted Stephen Strasburg. The right-hander, coming off a sensational 14-strikeout debut, will make his first road start Sunday in Cleveland.
Jake Westbrook (4-3) gave up two runs over 7 1/3 innings as Cleveland won for the fourth time in five games, depriving Washington of its first four-game winning streak.
Kearns hit a three-run shot off Luis Atilano (5-3) in the first inning. He hit the first pitch of the fourth for a 5-1 lead and his fourth multiple homer game, first since June 4, 2006, at Houston.
"Before we came in here I was glad to see him doing well," Nationals manager Jim Riggleman said. "I wish we had done a better job on him tonight.
"He's a strong man. Anytime he walks up there, he has a chance to do some damage and he did it."
Kearns holds no animosity toward the Nationals, who made him a free agent in November. He signed a minor league deal with Cleveland in January and is playing regularly with outfielder Grady Sizemore out for the year after knee surgery.
"It doesn't matter which team it is, I want to win, not just against them," he said.
The 30-year-old was limited to 80 games a year ago by a right thumb injury that required surgery in August. The previous year, he had right elbow surgery and played only 86 games.
Kearns' bid for a third homer was caught by leaping center fielder Nyjer Morgan at the wall in right-center in the seventh.
"I knew it was going to be close, but I'm not surprised Nyjer came up with it," Kearns said. "He can play."
Cleveland catcher Carlos Santana went 0 for 3 with one run and a walk in his big-league debut. The switch-hitter, who hit .310 with 57 homers and 265 RBIs in 317 minor league games, was called up from Triple-A Columbus -- and quickly tested on defense.
Morgan opened the game with a single and took off for second on the first pitch to Ivan Rodriguez. Santana, converted from an infielder to catcher in 2007, threw out the speedster with a quick, accurate throw.
"Wow," Santana said through an interpreter. "That felt good. I knew it was a team that could run."
Rodriguez then doubled and scored on a double by Adam Dunn for a 1-0 lead.
"Carlos' throw was huge," Westbrook said. "It would have been at least 2-0 without it. He was great back there all night."
Atilano, a rookie, allowed six runs over five-plus innings, dropping to 4-1 in six road starts. All three first-inning runs he allowed were unearned due to an error by second baseman Adam Kennedy.
Westbrook improved to 4-1 in seven starts since May 11. The right-hander, who missed much of 2008 and all of 2009 after having Tommy John surgery, struck out five. That was the most since he fanned eight in a complete-game win at Baltimore on May 16.
Acta was greeted warmly by several Nationals players during batting practice. Hired to his first big-league job in 2007, he received a few manager of the year votes that year before injuries took their toll in a 102-loss season in 2008. Washington was 26-61 at the All-Star break a year ago when he was dismissed.
Earlier this week, Acta refused to blame the Nationals for letting him go. He said he felt "grateful" that he was fired, because it gave him the opportunity to pursue the job in Cleveland after the Indians fired Eric Wedge at the end of a 97-loss season in 2009.
RHP Chad Ogea, winner of two games in the 1997 World Series, signed autographs before the game as part of the Indians' alumni program. ... Cleveland sent C Lou Marson to Columbus to make roster room for Santana. ... Morgan, Rodriguez and Dunn went a combined 6 for 9. The rest of the Nationals were a combined 1 for 21. Dunn has hit .339 (40 for 118 with seven homers and 21 RBIs since May 9. ... Kearns, Hafner and Jhonny Peralta were a combined 6 for 11 with five extra-base hits.