He has yet to match up this year with Felix Hernandez, who will try to avoid losing five straight starts for the first time as he returns for his first action in three weeks.
Wilson has won his last nine decisions and his teams have captured his last four matchups with Hernandez, as the Angels try to complete a three-game home sweep Sunday.
Wilson (17-6, 3.36 ERA) is trying to become the seventh Angels' pitcher to win 10 straight decisions. He's 9-0 with a 3.19 ERA in his last 13 starts, with victories in four straight.
The left-hander cruised Monday as he gave up one run in seven innings to earn a 12-1 victory at Oakland. He leads all major league southpaws in wins, and can become the first 18-game lefty winner for the Angels (76-78) since Jarrod Washburn in 2002.
Wilson is 3-0 with a 1.77 ERA in three starts against Seattle (67-88) this year, with Justin Smoak 0 for 7 with five strikeouts against him in those games. Former Angels teammate Kendrys Morales is 5 for 9.
This will mark the first 2013 outing for Wilson opposite Hernandez (12-9, 3.01), who has not pitched since Sept. 2 due to an oblique strain. Hernandez threw 58 pitches off the bullpen mound Thursday in Detroit.
"Felix was back to being Felix (Thursday)," pitching coach Carl Willis told the Mariners' official website. "He was strong, threw all of his pitches for strikes and had great command."
Hernandez has posted a 7.84 ERA while dropping four straight starts for the first time since April 27-May 13, 2008.
The right-hander is 2-1 with a 3.00 ERA in four outings against the Angels this year. It should be fun to watch him pitch to Mike Trout, who is 15 for 37 (.405) against him.
This will mark the sixth time these two have met as starters. Hernandez allowed one run in eight innings and Wilson pitched a six-hitter in Seattle's 2-1 victory over Texas on Sept. 17, 2010, in the first one.
Wilson has gone 3-0 with a 2.81 ERA in the next four meetings. 'King Felix' is 0-3 with a 5.19 ERA in those games.
Los Angeles has won five straight over Seattle thanks to a pair of one-run victories in this series. The Angels won 3-2 in 11 innings Friday and built a four-run lead before holding on for a 6-5 victory Saturday.
Trout's streak of reaching base in 26 straight games ended as he went 0 for 4 on Saturday. He has three homers and six RBIs over his last five games.
Los Angeles was officially eliminated from playoff contention Saturday despite winning for the 21st time in 28 games.
"I think the one word that still lingers out of all this clubhouse and how we all feel is certainly 'frustration,'" manager Mike Scioscia said. "I don't think there's been any way to sugarcoat it. It's obviously not a good feeling when you don't accomplish your goal."
Mariners rookie Nick Franklin is 5 for 8 with three runs scored in this series.