The Astros sent six players to the All-Star Game held at Progressive Field in Cleveland, the most in baseball, including four starters: Alex Bregman, Michael Brantley, Justin Verlander, and George Springer; pitchers Gerrit Cole and Ryan Pressly were also selected.

In his Astros debut on August 3, Sanchez tossed the first six innings of a combined no-hitter versus the Seattle Mariners, while Greinke was 8–1 with a 3.02 earned run average (ERA) over 10 starts for Houston.

On September 18, the Astros clinched a postseason berth against the Texas Rangers and became the first team since the 2002—2004 New York Yankees to produce three consecutive 100-win seasons.

For the first time in franchise history, the Astros led with the best regular-season record in baseball and defeated the Tampa Bay Rays in the American League Division Series (ALDS) by a margin of three games to two.

Despite the World Series upset, this Astros team is still considered to have put together one of the best regular seasons, and most talented rosters, in the history of baseball, owing largely to its historic 107-win campaign, earning the biggest share of season-end accolades, and record-breaking individual achievements.

Following the season, the Astros led the league with a record six players selected to 2019's inaugural All-MLB Team, including Altuve, Alvarez, Bregman, Cole, Greinke and Verlander.

Bregman and Springer were honored with AL Silver Slugger Awards, while Greinke was likewise named along with a Gold Glove based on his play in the National League.

On March 24, 2019, the Astros signed right-handed pitcher Justin Verlander to a two-year, $66 million contract extension to keep him with Houston through the 2021 season.

[6] In April 9 game against the New York Yankees, Jose Altuve connected for his 100th career home run off Jonathan Loáisiga in a 6–3 win.

[11] Alvarez became the fourth player in MLB history to hit four home runs in his first five career games when he homered off Clayton Richard of the Toronto Blue Jays, joining Trevor Story, Yasiel Puig and Mike Jacobs.

The only players in the divisional play era to reach the milestone faster were Ichiro Suzuki, Wade Boggs, Kirby Puckett, Nomar Garciaparra, Tony Gwynn and Derek Jeter.

From the Toronto Blue Jays, the Astros received right-handers Joe Biagini and Aaron Sanchez and minor league OF Cal Stevenson for OF Derek Fisher.

[18] On August 3, Sanchez and Biagini, both making their Astros debuts, tossed part of a combined no-hitter of the Seattle Mariners, along with Will Harris and Chris Devenski, to lead a 9–0 win.

He joined Nolan Ryan, Randy Johnson, Roger Clemens, Tom Seaver, Pedro Martinez, and Bob Gibson as the only pitchers with nine or more seasons of 200+ strikeouts.

He joined Cal Ripken Jr. and Alex Rodriguez as the only major league shortstops to hit 100 career home runs before their 25th birthday.

[24] Sanchez was removed from his fourth start for the Astros on August 20 after 2+2⁄3 innings due to pectoral muscle tightness, and later underwent surgery, prematurely ending his season.

[25] In the September 1 contest versus the Blue Jays at Rogers Centre, Verlander pitched his third career no-hitter, the second of the season for the Astros, and 13th in team history.

[26][27] On September 7, Verlander continued his domanance, reaching 32 consecutive batters retired, a streak that established an Astros franchise record and was tied by teammate Ryan Pressly in 2022.

The 15 strikeouts tied Verlander's Minute Maid Park record, set earlier in the season on June 12 versus the Brewers.

Robinson Chirinos and Yordan Alvarez each homered twice, and Alex Bregman, Jose Altuve, and Michael Brantley all added home runs to give the Astros a club record-tying seven in the game.

The 32 runs were second in major league history within a nine-inning span only to the 2007 Texas Rangers, which included a record 30–3 win over Baltimore, per the Elias Sports Bureau.