On November 3, 2021, the day following the ending of the World Series, seven Astros were declared free agents, including Carlos Correa, Yimi García, Marwin González, Kendall Graveman, Zack Greinke, Brooks Raley, and Justin Verlander.

Ably blending his experience and teaching with analytics, he coached Dallas Keuchel and Verlander in their Cy Young-winning seasons (2015 and 2019, respectively) and was credited with assisting Gerrit Cole and Charlie Morton in elevating their own success.

The National League adopted the designated hitter full-time, a draft lottery was implemented, postseason eligibility was expanded from ten teams to twelve, and advertising patches appeared on player uniforms and helmets for the first time.

Batting versus Mike Mayers in the seventh inning, he hit it 423 feet to left field while his parents, Cecilia and former major league second baseman Gerónimo Peña, were interviewed by Heidi Watney on Apple TV+.

Closer Ryan Pressly, pitching in back-to-back contests for the first time on the season, issued two walks in the tenth before Ketel Marte lifted a sacrifice fly to score Seth Beer for the game-winning run.

[39] The Astros placed Alvarez on the injured list on April 15 for "health and safety protocols," although manager Dusty Baker noted that he had not tested positive for COVID-19, but that "he's still feeling under the weather" since missing both games versus Arizona.

He made his major league debut on April 22 versus the Toronto Blue Jays, as a pinch hitter the ninth inning of a 4–3 loss, striking out in his lone at bat.

Justin Verlander took a no-hitter into the seventh inning, and Yordan Alvarez emptied the bases with a go-ahead double in the ninth as the Houston Astros defeated the Oakland Athletics, 5–4, to complete a three-game sweep.

In the ninth, Andrus realized a second RBI double of the game to close the gap to one for the A's, but Ryan Pressly induced a groundout from Bethancourt that stranded the tying run at second base for his 10th save.

[75] Due to left elbow discomfort, the Astros placed left-handed reliever Parker Mushinski on the 15-day IL on June 7 and recalled Brandon Bielak from Sugar Land to replace him on the roster.

[87] J. J. Matijevic, starting as the designated hitter, achieved his first major league hit—a home run—on June 19 versus Chicago White Sox starter Michael Kopech in the fourth inning, landing in the Crawford Box seats at Minute Maid Park, in a 4–3 Astros win.

Judge walked off the Astros for the second time in four days, hitting the game-winning three-run home run in the bottom of the tenth inning versus Seth Martinez (0–1) for a 6–3 final score.

With Yuli Gurriel batting, Yankees starter Luis Severino removed his PitchCom device and held the speaker to his ear, apparently unable to hear Jose Trevino's signals.

[105] Following a left knee injury to Jason Castro, the Astros selected the contract of catcher Korey Lee from AAA Sugar Land on July 1, 2022, and promoted him to the major league roster that day.

[107] On July 2, catcher Martín Maldonado, second baseman Jose Altuve, and starter José Urquidy led a 9–1 rout of Los Angeles as Houston delivered their 50th win of the season.

Taylor Clarke then relieved Garrett, who yielded a slowly-hit ground ball to Yuli Gurriel that snuck through the Kansas City infield to score Tucker and tie the game at 6.

The Astros infield appeared to have turned a routine double play, but the Royals challenged, contending that Jose Altuve failed to touch second base to eliminate the lead runner and his throw to first was late.

After Houston reliever Bryan Abreu walked home a run, he was removed in favor of Phil Maton, which resulted in Nicky Lopez hitting a fly ball to Alvarez in left field.

With two outs in the second inning, Yuli Gurriel and Jake Meyers hit consecutive singles before Chas McCormick walked to load the bases, and Maldonado followed with his drive versus rookie Jared Koenig (1–3).

[158] On August 7, Triston McKenzie (8~8, game score 85) tossed eight scoreless innings and catcher Luke Maile hit his first home run since May 20, 2019, as the Guardians handed Houston their 7th shutout loss of the season, 1~0.

Prior to the August 14 game versus Oakland, the Astros chartered 10 buses to transport approximately 500 family members and friends of the victimes of the Robb Elementary School shooting on May 24, 2022, in Uvalde, Texas.

Framber Valdez (12–4) delivered seven innings of two-run ball for his 20th consecutive quality start on August 17, tying Mike Scott's club record established during his Cy Young-winning season in 1986.

[178] Framber Valdez (13–4) authored a new franchise record 21st-consecutive quality start on August 24 versus the Twins, allowing two hits and one run in seven innings and getting eight strikeouts to lead a 5–3 Astros win.

In the series finale and last meeting with Oakland for the season, Valdez allowed two runs over six innings for a 25th consecutive quality start, surpassing deGrom's in-season record, as Houston won 11–2.

Former Astros pitching coach Brent Strom returned to Minute Maid Park in game action as a visitor for the first time since resigning his post with the club after the 2021 World Series.

Source: MLB Standings Grid – 2022 In Game 1 of the Division Series, Astros ace Justin Verlander surrendered six runs on ten hits in four innings, including a combined a 5-for-5 by Seattle's first two hitters, Julio Rodríguez and Ty France.

The Dodgers, winners of a major league-leading 111 games during the regular season, fell to the Padres in the National League Division Series, giving the Astros home-field advantage for as far as they could extend their playoff run in 2022.

Anthony Rizzo hit a solo shot off of Rafael Montero in the eighth and the Yankees threatened with a single by Giancarlo Stanton and two-out walk by Josh Donaldson to bring the go-ahead run to the plate.

Ryan Pressly was called on for the four-out save and struck out Matt Carpenter to end the eighth and finished the off the game with a perfect ninth to give the Astros a 1–0 series lead.

Luis García, making his first appearance since earning the win in the ALDS finale versus Seattle, allowed a home run in the top of the tenth inning to J. T. Realmuto that stood as the game-winner for Philadelphia, 6–5.