The left-hander appeared to have the right tempo and mechanics at the outset. He threw two scoreless innings to begin the game, and with two outs in the third, looked to be in control.
That was until he put a 90-mph fastball right down the plate for All-Star Albert Pujols, who ripped a single over the head of shortstop Jack Wilson to begin a two-out rally.
Third baseman Troy Glaus then singled, catcher Yadier Molina stroked a two-run double, and center fielder Rick Ankiel hit a deep blast to right-center field for his 20th homer of the season to put the Cardinals up quickly, 4-0.
"I threw a pitch right down the middle to one of the best players in the game," Duke said. "You just can't do that. I fell behind the next guy and kind of fell apart from there.
"I have to be able to take a step back and slow things down and just focus on executing pitches and getting that one out. I didn't do that tonight."
The Cardinals added to Duke's woes with another run in the fourth on All-Star Ryan Ludwick's home run to the bleacher seats in left field.
It was the second consecutive disappointing outing for Duke. On Sunday, he had the shortest outing of 2008 against the Brewers, when he gave up six runs on seven hits in only 2 2/3 innings.
Duke's line on Friday: Five runs on 10 hits in six innings.
"You get through that [third] inning and you never know what's going to happen," manager John Russell said. "Unfortunately, they got four runs and the way [Cardinals starting pitcher Kyle] Lohse was pitching, it was hard for us to come back."
Russell couldn't have been more right. The Pirates' offense struggled all night against one of the National League's biggest surprises.
The Pirates' best scoring chance came in fourth with the bases loaded and one out. However, Duke, who was batting eighth, struck out and Wilson lined out to center field to end the threat.
Lohse finished with only six hits in seven innings, including three strikeouts. He and Jaime Garcia, who was making his Major League debut, shut out the Pirates for only the third time this season.
"He threw the ball well," Russell said of Lohse. "We had a couple of chances earlier in the game to get him and he made good pitches to get out of it. He was pretty efficient. He changed speeds real well. His slider was working real well for him and he used it very effectively. He settled in and threw a really good game against us."
The only good news to come out of Friday's game for the Pirates was their bullpen. Paul Maholm's eight strong innings on Thursday, coupled with Duke's six, gave the bullpen some much-needed relaxation.
Russell only used relievers Denny Bautista and Sean Burnett on Friday, allowing workhorses Tyler Yates, John Grabow and Damaso Marte to rest.
"We'll be good for the next couple of days," Russell said.