Seeds one through three were determined by regular season winning percentages among division-winning teams (with any ties broken by head-to-head records).

The Houston Astros clinched the American League West on September 30[7] and secured the second-seed in the AL postseason with a 95–67 record.

[8] The Chicago White Sox clinched the American League Central on September 23,[9] and secured the third-seed in the AL postseason with a 93–69 record.

[15] Tampa Bay starter Shane McClanahan earned the win, pitching five innings while allowing five hits, no walks, and striking out three batters.

Houck got the win in relief for Boston, while Tampa Bay reliever Collin McHugh, who allowed three runs on two hits and a walk in 1+2⁄3 innings, took the loss.

[20] In the top of the eighth, Wander Franco homered and Randy Arozarena hit an RBI double, both off of Hansel Robles, as the Rays tied the game, 4–4.

After two scoreless innings, Boston scored five runs in the bottom of the third off Shane McClanahan, including a three-run homer by Rafael Devers.

After all five runs were scored from Boston, Shane was then taken out after 22⁄3 innings in frustration, throwing his glove and smashing a chair inside the Rays' bullpen.

An outfield assist by Kevin Kiermaier cut down Alex Verdugo at third base to end a Red Sox threat in the bottom of the eighth.

After the Red Sox put runners at second and third with one out in the bottom of the ninth, a sacrifice fly by Kiké Hernández pushed across the series-winning run.

Their previous postseason meeting was in the 2005 World Series, when the Astros were members of the National League, won by the White Sox in a four-game sweep.

The two men also spent a season together on the 1986 Athletics, when Baker was ending his playing career and La Russa was on his second managerial job.

Alex Bregman drove in what turned out to be the go-ahead run on a fielder's choice that scored Jose Altuve, who slid just by the catcher's foot and tag.

The Astros rallied for five runs in the seventh inning when eight batters went to the plate, with Yordan Alvarez hitting a liner past second base to break the 4–4 tie.

With two outs, Carlos Correa then lined a ball past right fielder Leury Garcia for a two-run double and Kyle Tucker capped the game with a home run.

With the Astros win, it marked the fifth consecutive Division Series in which they won the first two games, a feat matched by no team in the past 25 years.

[34] Dubiously, the White Sox became the first team in Major League history with at least 15 hits with none for extra bases in the first two games of a postseason, having accrued 18 singles.

Gavin Sheets homered in the bottom of the second to start the scoring, but the Astros would answer right back in the top of the third with a Carlos Correa bases-loaded double to bring it 2–1 and knocking Rodón out of the game.

Michael Brantley added two insurance runs with RBI singles in the sixth and eighth innings before Jose Altuve capped off the day with a three-run homer in the top of the ninth.

The nine-run victory was the largest winning margin ever recorded by a team in a clinching game of the American League Division Series.

[37] With the starts by Altuve, Bregman, Correa, and Yuli Gurriel, they played their 60th postseason game together, the most by a quartet of teammates in major league history.