Lackey couldn't hold a two-run lead, before he was kicked out by umpire Tom Hallion, and the Cardinals went on to a 4-2 loss to the Cincinnati Reds.
Todd Frazier drove in Chris Heisey with a single in the first, and Ryan Ludwick tied it for the Reds in the second with his ninth homer and first since Aug. 17 — a 374-foot shot into the left-field seats.
Lackey was ejected four pitches into the third inning.
"Lackey was told to quit arguing balls and strikes," Hallion said. "He continued to argue."
Lackey was surprised by the ejection.
"I'm not really sure," Lackey said. "I threw a ball that was up. I said 'That's up, the other one's not down.' He started yelling back toward me. I got back up on the mound and said 'Whatever.' There's no way he could have heard what I said. I didn't say any cuss words toward him.
"He saw my mouth moving and threw me out. It was unexpected, for sure. I've been thrown out a few times throwing balls at people, but never for something like this."
Cardinals manager Mike Matheny went out to diffuse the situation, but was too late.
"He's a guy that lets his emotions fly out there," Matheny said of Lackey. "He was frustrated on a couple pitches, one borderline high, one borderline low, that got him a little fired up. It wasn't the first exchange. The umpire took exception to it.
"The umpire told him no more, and he gave him more. We've seen that basically every start. Part of it is his intensity. We don't want to take the emotions out of it. We want them having that edge. Some umpires take it better than others."
Alfredo Simon shook off a rough start but lasted seven innings and drove in the go-ahead run with the second of his two doubles.
Terry Lyons (0-4) took the loss after Lackey was kicked out.
The Reds have won back-to-back games for the first time since Aug. 27-28 against the Chicago Cubs. The Central Division-leading Cardinals hadn't sustained consecutive defeats since a four-game losing streak from Aug. 26-30.
With the game tied 2-2, Jay Bruce led off the Reds' fourth inning with a bloop single. Simon, who entered with one career double, went the opposite way into the right-field corner to drive in Bruce with the go-ahead run.
Brandon Phillips added a bases-loaded, run-scoring single in the fifth to make it 4-2.
Simon (14-10) allowed five hits and two runs with three walks and five strikeouts for his second win in eight decisions over 11 starts since the All-Star break.
Simon retired the first two batters of the game before the Cardinals scored two runs. Matt Holliday walked and scored from first on Matt Adams' double. Oscar Taveras followed with a run-scoring single.
Cardinals: Matheny got no argument from SS Jhonny Peralta when the veteran was given Wednesday off. Peralta missed just three of St. Louis' first 145 games. "He wants to finish strong," Matheny said. "He's answered the bell."
Reds: RHP Pedro Villareal's status remained day-to-day after he was hit in the right forearm by Holliday's sharp one-hopper in the ninth inning of Monday's 5-0 loss.
Cardinals: Lance Lynn tries to improve to 4-0 in four 2014 starts against Cincinnati in Thursday's series finale.
Reds: Johnny Cueto will look to avoid dropping to 0-3 in three starts this season against St. Louis.
The ejection was the fourth of Lackey's career and first since 2009 when he was with the Angels and ejected two pitches into a game with Texas for throwing at Ian Kinsler.
The Cincinnati Reds acquired from Milwaukee minor-league RHP Kevin Shackelford and RHP Barrett Astin on Wednesday as the two players to be named in the Aug. 31 trade that sent RHP Jonathan Broxton to the Brewers.
OUT AT HOME
Bryan Pena was thrown out at home by Matt Holliday in the fifth inning. It was the 27th Reds runner thrown out at home this season without a force, pickoff, or caught stealing according to baseball-reference.com. The Dodgers are second with 25 runners thrown out at home.
Simon hit two doubles in the game. He is the first Reds pitcher to do that since Pete Schourek in September 1995 against Montreal.
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