The Series began on Wednesday, October 22, and (after weather delays had postponed the end of Game 5) concluded the following Wednesday, October 29. The American League's 4–3 win in the 2008 All-Star Game gave the Rays home field advantage for the series, meaning no more than three games would be played at the Phillies' stadium, Citizens Bank Park. The Phillies won their second championship in their 126-year history, taking the series four games to one and brought the city of Philadelphia a championship after 25 years. This was the first postseason series lost by a Major League Baseball team based in the state of Florida; previously, the Rays and Florida Marlins were 8–0 in post-season series.
The Philadelphia advanced to the World Series after defeating the Milwaukee Brewers and the Los Angeles Dodgers in the National League's Divisional and Championship Series, respectively. The team won its position in the playoffs after its second consecutive National League East title. This was the Phillies' first World Series appearance in fifteen years. The Tampa Bay Rays advanced to the World Series after defeating the Chicago White Sox and the Boston Red Sox in the American League's Division and Championship Series, respectively. The team earned its first trip to the postseason in franchise history after winning the American League East title, only one season after finishing in last place. Since each team had come first in its respective division during the regular season, this was the first Series since 2001 without a wild-card team.
The Philadelphia Phillies scored the first runs of the Series when Chase Utley hit a home run with Jayson Werth on base in the top of the first inning. The Phillies loaded the bases in the second inning, but were unable to score when Shane Victorino was thrown out at home plate by B. J. Upton. The Tampa Bay Rays loaded the bases in the bottom of the third inning; however, Upton grounded into an inning-ending double play and the score remained 2–0. The Phillies extended their lead when Carlos Ruiz batted in Victorino in the fourth inning. In the bottom of the inning, a solo home run from Carl Crawford pulled the Rays within two runs. The Rays added their second run the following inning when a double by Akinori Iwamura scored Jason Bartlett. Tampa Bay starting pitcher Scott Kazmir was removed after six innings; J. P. Howell and Grant Balfour combined to shut out the Phillies for 1⅓ innings. Ryan Madson relieved Phillies' starter Cole Hamels in the eighth inning, pitching a single perfect inning. In the top of the ninth inning, two Phillies' runners reached base. Tampa Bay's Trever Miller was brought on and threw four pitches—striking out Ryan Howard—before he was relieved. Philadelphia stranded two runners, on second and third base, and entered the bottom of the ninth inning ahead by one run. Philadelphia's Brad Lidge struck out the first two batters he faced and retired the third batter to get the save
Tampa Bay scored the first runs of the game in the first inning when Akinori Iwamura and B. J. Upton scored on consecutive ground outs by Carlos Pena and Evan Longoria respectively. The following inning Upton singled, scoring Dioner Navarro. Rocco Baldelli attempted to score from second base, but was thrown out by right fielder Jayson Werth, keeping the Rays lead at 3–0. Cliff Floyd extended the Rays lead to four runs after leading off the bottom of the fourth inning with a single, advancing to third base, and scoring on a Jason Bartlett sacrifice bunt. Rays starter James Shields shut out the Phillies through 5⅔ innings, before being relieved by Dan Wheeler who pitched an additional scoreless inning. Eric Bruntlett hit a home run in the top of the eighth inning to bring the score to 4–1. The Phillies added a second run in the top of the ninth inning, but were unable to score any more runs; Tampa Bay's win tied the Series at one game apiece.
The third game of the Series was delayed for an hour and 31 minutes because of rain. Country music star Tim McGraw, son of Phillies reliever Tug McGraw, spread his father's ashes on the pitching mound of Citizens Bank Park, prior to the game's start. The Phillies scored in the bottom of the first inning after Jimmy Rollins led off with a single and eventually scored when Chase Utley grounded out. In the next half inning, Tampa Bay's Carl Crawford doubled, stole third base and scored on a Gabe Gross sacrifice fly to center field. Carlos Ruiz gave the Phillies their second lead of the night when he hit a solo home run in the bottom of the second inning. Starting pitchers Matt Garza and Jamie Moyer pitched six and 6⅓ innings respectively. The 2–1 score remained unchanged until the sixth inning when Chase Utley and Ryan Howard hit the 14th back-to-back home runs in World Series history. Crawford scored his second run of the game in the top of the seventh inning when he was batted in by Gross again. Dioner Navarro continued the rally by scoring on a Jason Bartlett ground out—bringing the score to 4–3. In the top of the eighth inning, B.J. Upton led off with a single, stole second and third, and scored on a throwing error to tie the game. Eric Bruntlett was hit by a pitch leading off the bottom of the ninth, moved to second on a wild pitch and to third on a throwing error. Tampa Bay intentionally walked the next two batters to load the bases hoping to turn a triple-play and prevent a run from scoring, and brought in Ben Zobrist from right field to play as a fifth infielder in front of second base. However, Bruntlett scored the winning run on Ruiz's 45-foot infield single, the first walkoff infield single in World Series history, giving the Phillies a 2–1 lead in the series.
Philadelphia took a 1–0 lead in the bottom of the first inning, as Jimmy Rollins led off with a double and scored when Pat Burrell later walked with the bases loaded. The Phillies doubled their lead in the third inning when Chase Utley reached base on a fielding error and scored on Pedro Feliz's single. The Rays scored their first run when Carl Crawford hit a solo home run in the top of the fourth inning. Ryan Howard's three-run home run in the bottom of the inning brought the score to 5–1. Tampa Bay's Eric Hinske hit a pinch-hit home run to bring the Rays within three runs, but Phillies pitcher Joe Blanton responded with a home run of his own to re-extend the lead to four; it was the first time a pitcher hit a home run since Ken Holtzman in the fourth game of the 1974 Fall Classic. Blanton pitched six innings, giving up two runs on four hits to acquire his first win of the Series. Jayson Werth hit a two-run home run in the eighth inning—the Phillies third of the game—to bring the score to 8–2. Later in the inning Ryan Howard's second home run, and fifth RBI, increased the Phillies lead to eight runs. Philadelphia's four relief pitchers combined for three shutout innings, giving up one hit. Due to the late completion of the previous game, Games 3 and 4 each ended on the same calendar day.
Philadelphia scored in the first inning for the third consecutive game, taking a 2–0 lead when Shane Victorino batted in Jayson Werth and Chase Utley. Tampa Bay cut the lead in half in the fourth inning; Carlos Peña doubled and was batted in on Evan Longoria's single, both players' first hits of the Series. The Rays then tied the game in the sixth inning when B. J. Upton scored from second base on a Peña single. The game was suspended after the top of the sixth inning due to rain, making it the first game in World Series history not to be played through to completion or declared a tie.
After the game was suspended, umpiring crew chief Tim Tschida told reporters that he and his crew ordered the players off the field because the wind and rain threatened to make the game "comical." Chase Utley agreed, saying that by the middle of the sixth inning, "the infield was basically underwater." Rain continued to fall in Philadelphia on Tuesday, further postponing the game to Wednesday, October 29.
The game resumed with the Phillies batting in the bottom of the sixth inning. Pinch hitter Geoff Jenkins led off with a double and was bunted to third by Rollins. Jayson Werth then batted in Jenkins to take the lead for the Phillies, 3–2. In the top of the seventh inning, Rocco Baldelli re-tied the game at three runs with a solo home run. Later in the inning, Utley faked a throw to first, then threw Bartlett out at home for the third out in a play later described as having saved the Series for the Phillies. In the bottom of the seventh, Pat Burrell led off with a double. Eric Bruntlett, pinch-running for Burrell, scored on a single by Pedro Feliz to put the Phillies up by a run again, 4–3. In the top of the ninth, Brad Lidge gave up a single and a stolen base, but was able to strike out Eric Hinske to win the World Series for the Phillies.