The Pirates center fielder fouled off what would have been a sacrifice bunt in the seventh in an attempt to move Jack Wilson into scoring position. But instead, manager John Russell took the sign off the very next pitch, which allowed McLouth to hit a go-ahead, two-run homer.
The blast lifted the Pirates over the Yankees, 4-2, in front of the third-largest crowd (39,081) in PNC Park history.
"Sometimes it works out that way," McLouth said. "I messed up the bunt the pitch before. Luckily, I got a pitch ... and didn't miss it."
The home run, McLouth's 18th of the year, gave the Pirates their second victory over the Yankees this season, finishing their 2008 Interleague schedule 6-9. The game also concluded the two teams' three-game series, which saw the original finale postponed on June 26.
"You got to put [this win] right up there," Russell said. "The way we pitched, the way we played defense, the quality of at-bats that we had. When you play a team like that, you're going to have to do some good things to beat them."
Pirates left-hander Paul Maholm kept the Yankees off-balance with devastating offspeed pitches over eight gutsy innings.
"Almost everything was working," said Maholm, who was given a mulligan because of the June 26 postponement. In his start that day, the Yankees opened up the game with four straight doubles in what became a three-run first inning.
Maholm didn't allow that to happen on Thursday, shutting down New York through the first six innings.
But in the seventh, the southpaw ran into trouble after what should have been a 1-2-3 inning. Maholm picked up two quick outs, but he allowed right fielder Justin Christian and pinch-hitter Wilson Betemit to reach on singles.
Maholm then hit Derek Jeter on the shin on a 2-2 curveball to load the bases, and Bobby Abreu gladly finished the two-out rally with a hard single to right field to tie the score at 2.
Maholm buckled down and got All-Star third baseman Alex Rodriguez to ground out to third. McLouth followed with his home run in the bottom of the inning.
"Whenever Nate hit the home run, it was a big relief for me because I backed myself in the corner," Maholm said. "I had 0-2 with two outs. You can't feel sorry for yourself, because you got a future Hall of Famer [in Rodriguez] out there and you got to make your pitch."
Maholm's start was something the Pirates desperately needed. The bullpen had several arms that needed rest, which caused Russell to call Maholm's outing "phenomenal" and "outstanding". It also got the attention of Yankees manager Joe Girardi.
"He didn't give us many opportunities," the Yankees skipper said. "I thought his breaking stuff was outstanding. His curveball, his slider -- he had great location and he located his fastball as well. He's probably been their most consistent starter, and he showed why tonight."
Maholm improved to 5-1 in 10 starts at home this season. It was also the fourth consecutive time that Maholm went seven-plus innings.
The Pirates struck first in the third when Freddy Sanchez lined a single just out of the reach of Jeter at short, scoring Wilson.
The Yankees helped the Pirates score their second run when Jeter botched a double-play attempt, allowing McLouth to reach base. Then, catcher Jose Molina overthrew second when McLouth attempted to steal. He eventually scored on Sanchez's sacrifice fly.
Left-hander Damaso Marte picked up his fourth save of the season for the Pirates in the ninth.
When Maholm got the last out in the eighth, the sell-out crowd at PNC Park gave the left-hander a standing ovation.
"It was awesome," Maholm said. "It's something I hope we get a lot more frequently. That was definitely well worth it and much appreciated."
Todd Krise is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.