The Rays, with their off-season acquisitions and continued prospect development, fostered high hopes both within the organization and from analysts for the team to perform well during the 2008 season.

Pitcher David Price, the #1 pick in the 2007 Amateur Draft, made his spring training debut on March 8 (prior to the Elliot Johnson incident), accidentally hitting Francisco Cervelli on the arm before striking out 2 to get through the inning.

The initial starting rotation for the Rays was James Shields, Matt Garza, Andy Sonnanstine, Edwin Jackson and Jason Hammel.

Carlos Peña was bringing the lumber that made him a superstar in 2007, having six home runs in the first 20 games, but finished the month with 31 strikeouts, and had difficulty getting on base with a batting average of just .200.

[2] Closer Troy Percival was placed on the disabled list for precautionary measures following his removal from a game in which he felt tightness in his hamstring after striking out a batter and then falling to the ground.

[4] On June 5 the Rays were involved in a benches clearing brawl at Fenway Park with the Boston Red Sox following a series of events leading up from the previous night's game.

On June 27, it was announced that Iwamura's suspension was upheld, while Crisp's was reduced to 5 games, no longer making him the longest suspended player of all involved.

[8] On June 12, it was reported that Red Sox closer Jonathan Papelbon had made comments about the incident stating that in his opinion, it was "a bunch of bull what [the Rays] did.

Troy Percival was placed on the Disabled List once again on July 1, due to re-injuring his hamstring, this time after running to back up a throw to third base.

Andrew Friedman, Executive Vice President of Baseball Operations for the Rays, commented on the lack of trade activity saying, "At the end of the day we didn't find something that lined up for us.

[14] To make room for Bradford on the roster, relief pitcher Al Reyes, who was the Rays' closer from the 2007 season and had 26 saves in that role, was designated for assignment.

[20] Closer Troy Percival was removed from another game on August 14, because of a right knee sprain which he suffered from fielding a bunt and tagging the runner out.

By the end of the month, the Rays' entire starting rotation, Scott Kazmir, Matt Garza, Edwin Jackson, Andy Sonnanstine, and James Shields, had recorded at least 10 wins.

As Jason Bartlett stated, the Rays were "pumped" for the final month of the season, "no one wants to play us, especially at home,"[23] and the team was determined to prove that they were a legitimate post-season contender.

In Toronto for his second outing since his return, he allowed a walk-off grand slam with two outs when the Rays were ahead by a single run and in position to win the game in extra innings.

[26] Instant replay made its Major League Baseball debut at Tropicana Field on September 3 after Alex Rodriguez of the New York Yankees hit a ball near the left-field foul pole that was initially ruled a home run by third base umpire Brian Runge.

After a conversation among the umpires, though all agreed the play was ruled correctly, crew chief Charlie Reliford allowed the replay to take place and after review, upheld the home run call.

[29] He made his first career start against the Baltimore Orioles on September 22, pitching 5+1⁄3 innings, allowing four hits and two runs (one earned), while striking out three, but did not pick up a decision in the Rays 4–2 win that night.

Third baseman Evan Longoria made his return to the Rays as a starter on September 13 in the first game of a doubleheader against the New York Yankees, more than a month after being hit by a pitch in his hand, causing a fracture.

On September 18, it was reported that left fielder Carl Crawford would miss the rest of the regular season due to a finger injury suffered in the previous month.

[31] On September 26, despite losing that day, the Rays clinched their first ever AL East Division Championship when the Boston Red Sox lost to the New York Yankees.

With three balls and no strikes, Rays manager Joe Maddon gave Pena the green light to swing away, a move which backfired as Peña flew out to right field.

The Rays answered in their half of the 1st inning off Red Sox starter Josh Beckett, with a 2-out home run by Evan Longoria which also brought in Carlos Peña, evening the game at 2–2.

The Red Sox scored a run in the 8th inning, causing Rays manager Joe Maddon to pull starter Andy Sonnanstine.

In the bottom half of the 7th inning, with Rays starter Scott Kazmir having been removed from the game by manager Joe Maddon, the Red Sox began to rally.

Rocco Baldelli knocked a single into left field in the 5th inning, scoring Willy Aybar from second base and putting the Rays ahead for the first time in the game, 2–1.

Price returned to close out the game in the 9th inning, and after two strikeouts and a walk, Jed Lowrie hit a ground ball to Rays second baseman Akinori Iwamura, who stepped on second base to make the final out and send the Tampa Bay Rays to their first World Series in franchise history, defeating the Boston Red Sox four games to three.

Price finished the game, with the Phillies making it interesting by scoring a runner from second base because of an error by Rays' third baseman Evan Longoria, who deflected the ball into shallow left field.

In the 8th inning for the Phillies, Jayson Werth and Ryan Howard each hit 2-run home runs, finishing off the Rays in the most one-sided game the series had seen by a score of 10–2.

The team took eleven walk-off victories in the 2008 regular season,[33] and one in the postseason, four of which were home runs: In March 2008, the Rays announced Tropicana Field would host seven Saturday night postgame concerts featuring various artists.