Siegrist pitched a scoreless sixth, but he hit Anthony Rizzo with a pitch to start the seventh and Valbuena went yard two batters later.
Manager Mike Matheny said he wasn't worried about leaving Siegrist in for more than one inning, despite the fact that Siegrist hadn't seen Major League game action for almost two months. He was on the DL with a left forearm injury and later a nerve issue in his shoulder.
"It's part of why we let [Siegrist] stay down [in the Minors] and throw until he was a multiple-inning guy," Matheny said. "We had the matchups we wanted right there. We wanted him in that situation in that part of the lineup and a lefty ended up getting [to] him."
The Cardinals were on the verge of tying the game in the eighth with a runner on third and one out, but Cubs reliever Neil Ramirez shut the door by inducing a flyout in foul territory and striking out Matt Carpenter.
Siegrist was charged with his second loss, and it was the second time in the game that the Cardinals had surrendered a lead.
St. Louis tallied three in the first inning off Cubs starter Travis Wood, scoring on a Cubs' error and a two-run double from Jon Jay.
"I was doing the math in my head and calculating what my next move would be," Cubs manager Rick Renteria said. "Fortunately for us, I didn't have to do anything out of the ordinary."
Wood went five innings, throwing a season-high 113 pitches, and only two of the five runs he gave up were earned.
The Cubs came back with five runs against St. Louis starter Joe Kelly. Ryan Sweeney tied the game with a three-run shot in the second and added one more with an RBI single in the third. Wood hit his third homer of the season to lead off the fourth, tying him for the Major League lead among pitchers.
According to Matheny, Kelly struggled with his sinker, which ultimately threw off the rest of his repertoire during his 4 2/3 innings. He allowed five runs on eight hits with two walks and four strikeouts.
"You could tell at the top, [Kelly] knew they were going to be sitting on a good fastball," Matheny said. "He was trying to get a feel for his secondary [pitches], and just anticipating that his sinker would be there, and it wasn't as locked in as he wanted it to be."
The Cards' bats tied the game at 5 with solo shots from Carpenter and Matt Holliday in the fifth. Both went 3-for-5 with two runs scored on the day.
St. Louis took a 6-5 lead in the sixth when pinch-hitter Oscar Taveras singled to bring home Jay, who was nearly hit by the line drive to left.
Kelly was hit in his left elbow by a Matt Adams foul ball in the dugout in the third, and he was checked out by the medical staff, but went back out for the fourth.
"I tried to turn my head to get away from it," said Kelly. "It's got some seams. It's a little swollen, but it'll be all right."
The Cardinals will call on Shelby Miller -- making his first start since July 10 -- to snap their season-high four-game losing streak on Saturday.