Wilkerson had three homers and six RBI, both career highs, to help the Rangers beat the Los Angeles Angels 8-3 on Tuesday night.
Wilkerson had a three-run shot in the fourth, connected with the bases empty in the sixth and added a two-run homer in the seventh for his 13th of the season to become the first AL player with a three-homer game this season.
"It's one of those nights," Wilkerson said after the Rangers won for the ninth time in their past 13 games. "You don't plan on doing it. I was hitting pretty much everything. I'm having a lot of fun. You don't expect to do that. I got pitches I could drive. I just got them in the air to right field."
Wilkerson also had a three-run homer on Monday night against Boston, hit a three-run homer against Detroit last week and has 15 RBI in his past seven games.
"He's been saving us with RBI and clutch hits," Rangers manager Ron Washington said. "He's a professional hitter."
Alfonso Soriano of the Chicago Cubs and Carlos Lee of the Houston Astros have three-homer games in the NL.
Rangers starter Kevin Millwood (5-7) gave up two runs and five hits in eight innings, striking out four with no walks in his longest outing of the season.
Millwood was in command from the second through the sixth, retiring 13 in a row before Vladimir Guerrero's leadoff double in the seventh.
"We're finally pitching the way we're capable of," Millwood said. "The first two months we stunk. Right now, everyone is starting to catch their stride."
The Angels had won six of the first seven meetings with Texas this season by a total of 42-22.
Los Angeles has lost five of its past seven overall, but manager Mike Scioscia said he isn't concerned.
"We've been playing at a high level for so long that you're going to hit a few bumps in the road," he said.
Los Angeles took the lead in the second on Howie Kendrick's two-run single.
Angels starter Ervin Santana (5-9) had a career-high 11 strikeouts in 5 1/3 innings, but left trailing 4-2 after throwing 111 pitches. Santana allowed five runs and seven hits, walking two.
One of his strikeouts proved costly as Marlon Byrd reached first on a wild pitch after going down swinging to lead off the fourth. Frank Catalanotto singled and both runners advanced on Gerald Laird's sacrifice bunt.
Wilkerson followed with his first homer of the game to give the Rangers a 3-2 lead.
Wilkerson added a solo shot in the sixth. The Rangers added another run in the inning when catcher Jose Molina's pickoff throw to third hit Texas runner Desi Relaford for the Angels' third error of the game. Relaford scored when the ball rolled into left field.
Scioscia has tried to get Santana to be more aggressive, and the right-hander did throw more strikes.
"I don't know what's going on," Santana said. "I tried to be aggressive. I felt good. I made two mistakes (to Wilkerson), that was it, a changeup over the middle and a backdoor curveball."
In the seventh, Catalanotto's sacrifice fly and Wilkerson's two-run homer off Chris Bootcheck extended the Rangers' lead to 8-2.
The last Ranger with three homers in a game was Mark Teixeira on July 13, 2006, at Baltimore. Wilkerson became the 14th Texas player with a three-homer game.
Guerrero scored on a Frank Francisco wild pitch in the ninth inning for the game's final run.
- Wilkerson's previous career highs were two homers and four RBI.
- The Rangers announced the signing of two draft picks: RHP Evan Reed (third round, Cal Poly-San Luis Obispo) and OF Tim Smith (seventh round, Arizona State).
- Santana's previous career high was 10 strikeouts on April 25, 2006, against Detroit.
- Rangers bench coach Art Howe was ejected by home plate umpire John Hirschbeck in the eighth inning for arguing from the dugout.