He gave up just one hit in his last four innings. By then, the damage was done.
"In the first two innings, when I got ahead of hitters, I didn't make the pitch to put them away," said Pineiro. "I didn't make them hit my pitches."
Pineiro had gone 3-0 with a 2.22 ERA in four previous starts against Cincinnati.
The Reds roughed up Pineiro despite playing with two main cogs -- Joey Votto and Brandon Phillips -- out of the lineup with the flu.
"Joel didn't have good command of his offspeed pitches," said Cardinals manager Tony La Russa. "There were a lot of pitches that missed location. He just wasn't sharp."
Meanwhile, Reds starter Johnny Cueto was dominant, allowing just one run on five hits through seven innings. Cueto (3-1) led all NL rookies in strikeouts last season.
"He's a different pitcher than last year," said Albert Pujols, who did not reach base for the first time this season. "He's locating better. Keeping the ball down. This year, he's a pitcher not a thrower. He's got that one year under his belt now. It's paid off for him."
The formerly homer-happy Reds played small-ball Friday night, with six of their first seven hits off Pineiro being singles.
The only extra-base hit was Jerry Hairston Jr.'s RBI double in the first inning. That knock scored Willy Taveras from first to put the Reds ahead, 1-0.
A bloop hit by first baseman Ramon Hernandez drove home Hairston to make the score 2-0.
The Cardinals hit the ball hard off Cueto in the first two innings, but to no avail.
They sent four balls to the warning track. Laynce Nix made a leaping grab of Khalil Greene's drive against the left-field wall to end the second inning.
With runners on first and third in the second, Pineiro fielded Cueto's sacrifice bunt, but he threw wide past first to allow Adam Rosales to score from third, giving the Reds a 3-0 lead.
"The ball just sailed away," said Pineiro. "I just hurried the throw. The ball was a little wet, but that's no excuse."
Taveras and Hairston each collected RBI hits to make the score 5-0.
Chris Duncan, Yadier Molina and Greene began the seventh with singles to load the bases. But the rally lost steam when Joe Thurston grounded into a 4-6-3 double play scoring Duncan but ending the offense's momentum. .
The run ended Cueto's scoreless streak at 15 innings, which dated back to April 27.
The Cardinals were caught napping in the seventh.
Paul Janish was thrown out attempting to advance on Cueto's sacrifice bunt attempt.
Assuming time had been called, Thurston held the ball, and Cueto ran to an uncovered second base. He advanced to third on a wild pitch moments later and scored on Jay Bruce's RBI single for a 6-1 Reds lead.
Tyler Greene hit his first Major League home run, a solo shot as a pinch-hitter in the eighth, igniting a brief Cardinals' rally.
Greene was pinch-hitting for Colby Rasmus, making it the first pinch-hit homer for the Cardinals this season.
As Weathers jogged in from the bullpen, hitting coach Hal McRae gave Greene some advice.
"Hal told me to look for a first-pitch fastball," Green said. "I got one over the middle of the plate. I put a good swing on it. It felt good."
Duncan's double to the wall in right-center scored Ryan Ludwick to pull St. Louis to 6-3. Molina then delivered an RBI single to bring home Duncan.
Weathers allowed three runs on three hits in one-third of an inning.
A potential ninth-inning rally was stalled when Thurston, who had led off by drawing a walk from Reds closer Francisco Cordero, was thrown out attempting to steal.
Cordero notched his ninth save.
"I gave the sign," said La Russa. "He got a bad jump. Put it this way, if it's a bad play, it's my bad play."