Nelson hit his first two home runs of the season, including a grand slam against his former team, to send Wilson and the Angels past New York 8-4 on Thursday.
"It's a great day for Chris, both offensively and defensively," Los Angeles manager Mike Scioscia said. "It's good to see his bat come alive. He's got some pop and he hasn't really shown it this year in the 100 or so at-bats he's had, but you saw it today and hopefully it's a sign of more to come."
Josh Hamilton and rookie J.B. Shuck each had an RBI single to help the struggling Angels prevent a four-game sweep. Wilson (13-6) won his fifth consecutive decision, keeping Alfonso Soriano in the ballpark after the streaking slugger piled up four homers and 13 RBIs the previous two nights.
Soriano extended his sensational tear, going 4 for 5 with an RBI single, but the Yankees managed little else until a three-run ninth as their four-game winning streak ended. After finishing a 5-2 homestand, they head to Fenway Park this weekend to face first-place Boston.
Nelson spent a couple of weeks with the Yankees in May, one of several replacements they tried at third base while Alex Rodriguez was recovering from hip surgery. A top-10 draft pick by Colorado in 2004, he didn't leave much of an impression -- until returning with Los Angeles.
"He hurt us bad today," New York manager Joe Girardi said.
Nelson hit a solo homer off Phil Hughes (4-12) to make it 3-1 in the fourth. He added his first career slam off Boone Logan in a five-run eighth for his first multihomer game in the majors. Mike Trout got the inning started by hustling for a pop-fly double that was misjudged by center fielder Brett Gardner.
The only time the Angels retired Soriano, it came on a nice play at third by Nelson, who started a critical double play earlier in the game. Shuck also threw out Soriano trying to stretch a single in the first.
"Everything just fell in place for me," Nelson said.
Wilson worked around 11 hits and threw a season-high 124 pitches in 6 2-3 innings while matching his win total from last year. The left-hander limited the Yankees to one run after they totaled 25 the previous two nights, improving to 9-1 with a 2.76 ERA in his last 12 starts.
The run began with a win over New York at home on June 14. He is 6-0 in his last seven road starts and 3-0 with a 2.08 ERA in five career starts against the Yankees, who outhit Los Angeles 15-11.
"It just only matters that I got through it," Wilson said. "We'll take any wins we can get right now. I was lucky to give up mostly singles, and that prevented them from having the big innings."
Wilson came in leading the majors with an average of 110.4 pitches per start and needed 71 to get through three innings. It could have been more, too, but he got Vernon Wells to ground into an inning-ending double play with the bases loaded after the Angels botched a popup.
That was the turning point for Wilson, who held New York in check on 53 pitches over the next 3 2-3 innings.
Hughes had his best outing in more than a month, throwing 73 of 104 pitches for strikes over six solid innings. But a brief hiccup put him behind in the fourth, and the Yankees never recovered.
The right-hander dropped to 0-5 in his last seven starts. He has lost 10 of his past 12 decisions and is 1-9 this season at home, where he's given up 17 of his 23 homers.
"I thought he threw the ball better today. I thought his command was better today, and he needs to keep improving," Girardi said.
Erick Aybar hit a leadoff double in the fourth, advanced on a passed ball and scored on Hank Conger's sacrifice fly. Nelson then fouled off four straight full-count pitches before sending an opposite-field drive into the right-center bullpen for his first home run since Sept. 14 with Colorado.
Scioscia said Nelson is a candidate for the third base job next year.
"I just want to make my mark," Nelson said.
He also reflected on his brief stint with the Yankees.
"Trust me, I enjoyed my time here. I enjoyed the guys and it was a great experience for me," he said.
Hamilton's two-out RBI single put Los Angeles up in the first after Shuck singled and stole second.
Moments later, Soriano socked a line drive off the left-field wall. But he jogged out of the box and was thrown out at second on a fine play by Shuck.
Gardner tripled in the third and scored when Soriano singled through a drawn-in infield for his 14th RBI in three days.
NOTES: Rodriguez went 2 for 5 while starting a day game after a night game for the first time since coming off the disabled list. He was rested last weekend under similar circumstances. ... Aybar was back at SS after sitting out Wednesday. He left Tuesday night's game with cramping in his left calf.