The Mets had no answer for Cubs starter Travis Wood, who entered with just one win this year. Wood held the Mets scoreless through seven innings, allowing five hits with six strikeouts.
Wood left after Adrian Cardenas pinch-hit for him to lead off the seventh inning against Mets reliever Jon Rauch. David Wright couldn't handle Cardenas' popup in front of home plate, allowing him to reach third base on the error.
"I thought I had it," Wright said. "I misjudged the wind a little bit. It's my call. If I think I can catch it, I call him off, and I did that."
Wright said the combination of the Mets playing poorly, the Cubs playing well, the early morning arrival and the emotional plummet after playing their in-state rivals culminated in a sloppy performance.
"We know we have to take care of business after the Subway Series as well," Wright said. "You get emotionally charged for the Subway Series, and you have to try to bring that same intensity before it and after it. We didn't do that today."
Two batters later, Darwin Barney hit a soft fly ball to right field that ricocheted off a sliding Lucas Duda, as Barney also went all the way to third. Second baseman Ronny Cedeno committed the third error on a grounder by Starlin Castro in the next at-bat, allowing Barney to score.
Rauch surrendered four unearned runs without allowing a hit in a third of an inning.
"When we talked earlier today, everyone was fine," Santana said. "But it was a tough night last night, so I don't blame them. It's just one of those days where things didn't work out."
Duda also went 0-for-4, snapping a streak of 25 straight games reaching base safely, dating back to May 27.
"Lucas has done his absolute best," Collins said. "Once in a while, because he's not a right fielder, you're going to have a hiccup. You hope they're not very many, and there haven't been."
Santana, who was going for three straight wins for the first time since May 2009, allowed five hits in six innings. He said he's getting the feeling for his changeup, which has been key to his success.
Santana stranded three runners on base through the first two innings and threw a perfect third inning before allowing his second two-out walk of the game in the fourth to catcher Geovany Soto. The Cubs took advantage of the free pass, as center fielder Joe Mather immediately followed with a two-run home run.
"The little things made the difference," Santana said. "That was the difference tonight. One little pitch or one little mistake can change the whole ballgame."
The Mets had just three hits through the first six innings, including a single by Wright that increased his hitting streak to 15 games. They recorded their lone run on a solo homer with two outs in the ninth inning by Ike Davis.
Wright said Wood threw two different fastballs and stayed in the zone where he wanted to all night.
"He threw a ton of strikes," Wright said. "You try to go up there and put the ball in play early. We hit it at somebody. If you go up there and take pitches, you're down 0-1, 0-2."
Opposing left-handed hitters were hitting just .203 against Santana, so the Cubs sat regular left-handed starters Tony Campana, Bryan LaHair and David DeJesus. The only lefty in the starting lineup was Luis Valbuena, who smacked a double in his first at-bat.
Santana redeemed himself against Valbuena in the sixth, when he forced the third baseman to ground out to second base with the bases loaded. The Mets starter has allowed just seven earned runs in 33 1/3 innings in his career against the Cubs.
"It was a tough night," Santana said. "It was a little windy, trying to get the feeling for the ball, a little dry, other than that, tried to battle and keep the ball down. It came down to a couple pitches that changed the whole ballgame for me."