Santana's most recent win came on Thursday in Boston where he held the Red Sox to a pair of runs and four hits in seven innings to run his record to 13-8 on the year to go along with a 3.93 earned run average.
Extending that streak may not be a problem tonight, as the right-hander has won all three of his home starts against the Rays, while pitching to a 1.21 ERA. He is 4-4 lifetime against them with a 5.17 ERA in 10 starts.
The Rays moved back into a tie atop the American League East standings with a win in the opener of this set on Monday, as James Shields pitched six-plus innings and fanned 10 batters helping Tampa Bay 4-3.
B.J. Upton hit Scott Kazmir's first pitch of the game over the wall in left field. Upton finished with two RBI for the Rays, who won for the eighth time in 10 games and are tied with the Yankees atop the division. New York lost in Toronto, 3-2, earlier Monday.
Shields (12-11) surrendered eight hits and three runs -- two earned -- to win for the fifth time in his last seven starts. Rafael Soriano struck out the side in the ninth to get his major league-leading 38th save.
"We scored three out of the gate and I was able to go deep in the game," Shields said. "I had good command of my fastball as well as my change-up. I got into a nice rhythm. Every win now is pretty big."
Kazmir (8-11), who broke into the majors with Tampa Bay in 2004 but was traded to the Angels in August of last year, suffered yet another loss, his sixth over his last eight starts. The lefty was touched for five hits and four runs -- three earned -- in 5 1/3 innings.
"Giving up three passes in the first inning is a recipe for disaster," Kazmir said. "If I would have gotten by the first inning, it could have been a whole different outcome. It was frustrating."
Hideki Matsui stroked a two-run double for the Angels, who lost for the sixth time in eight games.
The Angels will take their swings tonight against the returning Wade Davis, who because of a shoulder strain will be pitching for the first time since August 5. He had won his last four decisions before going on the disabled list and is 9-9 on the year with a 4.45 ERA.
This will be Davis' first-ever start against the Angels.
The Rays took two of three from the Halos earlier in the year.