Despite his past playoff experience, LHP Andy Pettitte did not appear overly calm or collected when he took the mound for the Astros against the Cardinals in Game 5 of the NLCS. After his fourth pitch struck SS-R David Eckstein in the left elbow, he issued a five-pitch walk to CF-L Jim Edmonds. However, St. Louis helped him out of the jam as 1B-R Albert Pujols popped out on the first pitch he received, LF-R Reggie Sanders flew out to left on his first pitch, and RF-L Larry Walker grounded out on his second pitch.

Leading off the bottom of the first, 2B-R Craig Biggio hit a soft grounder up the middle. 2B-R Mark Grudzielanek was unable to field the ball cleanly behind second base, so Biggio arrived at first without a throw. CF-R Chris Burke then laid down a sacrifice bunt to move Biggio to second. LF-S Lance Berkman worked RHP Chris Carpenter for an eight-pitch walk, and the runners advanced to second and third when 3B-R Morgan Ensberg grounded out. With the force now only at first, 1B-L Mike Lamb hit a grounder down the third base line, where 3B-R Hector Luna was playing way off the line. However, Luna hustled over to make the stop and executed an impressive throw to retire Lamb at first.

One out into the second and after fouling off six consecutive pitches, C-R Yadier Molina found his pitch and hit a flyball into deep right centerfield for a double. His efforts went unrewarded as St. Louis left him stranded at second.

RF-R Jason Lane opened the bottom of the second with a ground ball hit hard into left field for a single. C-R Brad Ausmus then knocked a grounder down the third base line and into left where it hit the edge of the stands where they angle out toward the field. Eckstein ran over to recover the ball as Sanders was playing deep and off the line. Lane moved to third on the double. Following a strikeout from SS-R Adam Everett, Pettitte hit a soft grounder to first. With Molina standing in front of the plate, Pujols threw home. Molina turned and applied the tag to Lane's shins as he began to slide. Lane's knee collided with Molina's mask and the tag tripped up Lane, so both players were knocked to the ground a bit dazed. With Ausmus at third and Pettitte at first, Biggio hit a line drive into left for a single that drove in Ausmus and moved Pettitte to second. When Burke foul tipped the first pitch of his at-bat, it bounced off the edge of Molina's glove and struck the fingers of his bare hand, leading to a brief visit from the Cardinals' trainer. Carpenter struck out Burke to close the inning before Houston could increase their 1-0 lead.

Hitting leadoff in the top of the third, Eckstein fouled a ball off the inside of his left knee, causing him to fall down, consult with the trainer, and hop around a bit before returning to the batter's box. He then hit a fly ball into shallow centerfield for a single. With Edmonds at the plate, Eckstein stole second without eliciting a throw. When Edmonds hit a line drive into right field for a single, Eckstein advanced to third. Pettitte looked like he might escape the inning cleanly as he struck out both Pujols and Sanders and put a 2-2 count on Walker, but true to his name, Walker took the base on balls. With the bases loaded, Grudzielanek dropped a soft flyball into right field for a single that drove in Eckstein and Edmonds while moving Walker to third. Pettitte then struck out Molina to take the game into the bottom of the third with St. Louis up 2-1.

Neither Carpenter nor Pettitte allowed any baserunners in the bottom of the third or top of the fourth respectively. In the bottom of the fourth, an inside pitch caught leadoff hitter Lane on the back of his left thigh. Ausmus then hit a grounder to Luna, who threw to second to get the force on Lane. Up next, Everett hit a groundball into right field for a single, moving Ausmus to second. Pettitte laid down a sacrifice bunt to advance the runners to second and third, but Sanders snatched Biggio's line drive from the air in left to end the inning before the Astros could score.

Two outs into the bottom of the fifth, Sanders hit a groundball into left field for a single. With Walker at the plate, Sanders stole second without inspiring a throw, however Walker grounded out to end the inning, stranding Sanders at second. Carpenter gave up a single to Berkman in the bottom of the fifth, but struck out Burke, Ensberg, and Lamb to move the game to the sixth. Leading off the sixth, Grudzielanek hit a groundball down the third base line into left field. Like Ausmus's hit earlier in the game it bounced off the stands, but Berkman was able to recover it quickly and throw to second where Biggio tagged out Grudzielanek, who unwisely tried for a double. Molina hit a line drive into left for a single, but the bottom of the Cardinals' line-up failed to drive him in. Carpenter retired the side without allowing a baserunner in the bottom of the sixth.

Up first for the Cardinals in the top of the seventh, Eckstein hit a grounder to short and should have been out at first, but Everett's throw forced Lamb to jump up off the bag to keep the ball from flying over his head and by the time he landed Eckstein was safe. The play earned Everett an error. With Edmonds at the plate, Houston caught Eckstein trying to steal second. Edmonds then hit a ball off one of the beams high above third base in foul territory, so while Houston caught the ball when it came down, his at-bat continued due to the ground rules of the stadium. He next sent a line drive up the middle, where Biggio cleanly fielded it and threw to first. This time the throw was good, but Lamb wasn't on the bag, so Edmonds was safe at first on an error by Lamb. After the play, the Astros called for RHP Chad Qualls to relieve Pettitte. When the game resumed, Edmonds advanced to second when Pujols grounded out down the third base line. Edmonds remained stranded at second when Sanders also grounded out.

The errors continued after the Cardinals took the field. One out into the top of the seventh, Biggio hit a groundball to Luna at third, but Luna bobbled the ball, allowing Biggio to reach first on his error. Up next, Burke hit a grounder into right field for a single that advanced Biggio to third. Biggio's hustle proved unnecessary when Berkman slapped the first pitch of his at-bat over the wall in left field to put Houston up 4-2. Ensberg followed, hitting a flyball off the scoreboard on the left field wall. Sanders bobbled it for a moment as he played it off the wall, but he recovered and threw to second in time for Grudzielanek to tag Ensberg, who was trying for two. The Astros' rally ended with Lamb flying out to center.

LHP Mike Gallo relieved Qualls prior to the start of the eighth. Gallo threw one pitch; Walker hit a grounder up the middle; Gallo batted it away with his glove then retrieved the ball and threw to first to retire Walker. Houston then called for RHP Dan Wheeler to close out the inning. Going into the bottom of the eighth, St. Louis replaced Carpenter with closer RHP Jason Isringhausen, who retired the side without allowing any baserunners.

Astros' closer RHP Brad Lidge took the mound in the top of the ninth. Lidge opened the inning by striking out left-handed hitter John Rodriguez, who was hitting for Luna. RF-L John Mabry also fell to strikes, leaving the Cardinals with one out between them and the loss of both the game and the series. With the count 1-2, Eckstein hit a grounder past a diving Ensberg and into left field for a groundball single. On the first pitch of Edmonds' plate appearance, Eckstein stole second without eliciting a throw. Lidge issued a five-pitch walk to Edmonds, bringing Pujols to the plate. Pujols took a pitch before sending the ball soaring through the air and off the windows high above left field for a three-run homer that put the Cardinals up 5-4. Lidge struck out Sanders to end St. Louis' drive, but the Astros were unable to move against Isringhausen in the bottom of the ninth, so the Cards took Game 5, extending the series and sending play back to St. Louis.