Cruz signed with the St. Louis Cardinals straight after graduating as a four-sport star at Arroyo High School in 1966. Years of minor league play resulted in him entering the majors as a September call-up in 1970, where he played six games and had six hits. The following year, he was called back up to the Cardinals on June 28, where he would play in 83 of the next 85 games primarily as a center fielder, batting .274 with a .377 on-base percentage (OBP), nine home runs, eighty hits, 49 walks, and 35 strikeouts.

The next year, he was the starting center fielder for the Cardinals on Opening Day. He would play in 117 of 156 games, which included a slump where he batted below .200 the whole month of June. He finished with a .235 average with 23 RBIs and 78 hits (both down from before) while having more strikeouts than walks. The next year, he played in 132 games for the team, where he batted a .227/.310/.379 line with 92 hits and 57 RBIs while also having 66 strikeouts (the most he would have for four seasons) and 51 walks. 1974 proved to be his last year with the team. He played in 107 games, with his .261/.341/.416 (batting average/OBP/slugging percentage) being his second best of four full years with the club. His career took an upswing when he was sold to the Houston Astros on October 24.

He made his debut for the Astros for their Opening Day start in 1975 as the right fielder and proved key in a 5-2 win with a key three-run home run in the fifth inning to break a 2-2 tie that led to a win for the team as he went 3-for-4.^[5][6] In 120 games, he batted .257/.358/.403 while garnering 81 hits, 52 walks and 44 strikeouts (the first of five seasons where his strikeouts weren’t higher than his walk count). After the Astros posted an 81–81 record in 1974, the team traded first baseman Lee May to the Baltimore Orioles, which allowed Astros left fielder Bob Watson to move the first base, opening the left field position to Cruz or teammate Greg Gross. By 1976, Cruz had secured the left field spot (although he would play right field for 1977 and 1978). With the exception of the late Roberto Clemente, Cruz was arguably the most famous baseball player in Puerto Rico during his playing career.

It was 1980 that proved big for Cruz and the Astros. In 160 games for the team, he would hit .302/.360/.426 while garnering a selection to the 1980 Major League Baseball All-Star Game, the first ever for him. His efforts proved key to the Astros making the postseason for the first time in team history. To get to the postseason, the Astros had to win a tie-breaker game with the Los Angeles Dodgers. In the first inning, he helped to score the first run of the game after hitting a ball that got him to first base on a fielder’s choice while scoring the runner on third base.^[7]

The 1980 National League Championship Series against the Philadelphia Phillies proved a close series (all but Game 1 went to extra innings), and Cruz proved important in numerous games. In Game 2, he broke a 2-2 tie with an eighth inning single to score Joe Morgan. When the Phillies came back to even it, he stepped up in the tenth inning with runners on first and second on one out with a single that was the first of four runs in the inning as the Astros evened up the series.^[8] In the do-or-die Game 5, he scored the first run of the game on a two-out double in the first inning. An intentional walk in the seventh with two outs proved important as the Astros scored three runs on two subsequent hits and a wild pitch that scored Cruz. While the Phillies made up for it in the top of the eighth inning to lead 7-5, Cruz and the Astros fought back to tie in the bottom half, as Cruz helped score the tying run on a two-out single. However, the Astros could not hang on for the tenth inning, as Garry Maddox scored in the winning run on a two-out double to seal the fate of the Astros (who had lost the last two games needing just one more win for the pennant).^[9] On the whole, Cruz batted .400 with four RBIs, six hits, eight walks, and one strikeout.

He continued some of his success with the following year. He played in 107 games (out of 110 possible games, owing to the strike) while batting .267/.319/.425 with 109 hits and 55 RBIs while having his second of four straight years with more strikeouts than walks (49 to 35). Despite this, he finished 14th in MVP voting as the Astros found ways to manage the strike-shortened season by winning the second half of the year and advancing to play the first half winner Los Angeles Dodgers. In the 1981 National League Division Series, he batted .300 in five games while having six hits and one stolen base, although the Astros would blow a 2-0 series lead by losing the next three on the road.

In 1984, he continued his successes with the team. He played in 160 games once again while batting .312/.381/.462 and having 95 RBIs, 22 stolen bases, and 187 hits. He reversed his troubles with strikeouts, having 73 walks and 68 strikeouts while leading the league in sacrifice hits with ten. He finished eighth in MVP voting while winning his second and last Silver Slugger Award. He was named player of the month for July, having raised his batting average from .266 to .313 in 29 games played.^[10]

The Astros returned to the postseason in 1986. While Cruz would bat in all six games, he only hit .192 with just five hits and two RBIs. 1987 was his final year with the Astros. He played in 126 games (the lowest in a full season since 1976) while batting .241/.307/.400, including 88 hits and 38 RBIs while walking 36 times and striking out 65 times.

He signed with the New York Yankees in 1988. He played in 38 games before being released on July 22. He had a .200/.273/.263 line with seven RBIs and eight strikeouts/walks. He had a total of 165 home runs and 1,077 RBI during his career, while hitting for a .284 batting average.

Cruz was involved in the Astros’ first nine postseason appearances: three as a player (1980, 1981 and 1986) and six as a coach (1997–1999, 2001, 2004–2005). As a player in the postseason, he hit .400 in the five-game series against the Philadelphia Phillies in the 1980 NLCS. Cruz represented the Astros in the MLB All-Star Game in 1980 in Los Angeles and 1985 in Minnesota. He finished third in NL MVP voting in 1980, sixth in 1983, and eighth in 1984. He won the NL Silver Slugger Award as an outfielder in 1983 and 1984. In 1983, Cruz led the NL in hits with 189.

Cruz had played in more games than any other player in the history of the Houston franchise (1,870) before being passed by Craig Biggio in 2001. In 2000, Cruz coached from first base as Biggio surpassed many of his other long-standing franchise records, including at-bats, hits, and total bases. His eighty triples remains an Astros’ record, as does his six career walk-off home runs. His last home run, on July 17, 1988, was a pinch-hit grand slam against the Chicago White Sox in a 7–4 loss.^[11]

Post-playing career[edit]

On October 3, 1992, Cruz was honored by the Astros when the team retired his number 25; Cruz’s former teammate Mike Scott had his number 33 retired at the same time. In 1999, Cruz was selected by a panel of experts as one of three outfielders on the All-Astrodome team. In 2003, he was inducted into the Texas Baseball Hall of Fame. In 2018, the St. Louis Post-Dispatch determined that of players who spent at least five seasons with the St. Louis Cardinals that Cruz ranked eighteenth in all players in wins above replacement ahead of Hall of Fame players like Ted Simmons, Lou Brock, and Dizzy Dean.^[12]

After retiring from baseball, Cruz managed in both the Texas–Louisiana League and the Puerto Rican Winter League before returning as first base coach for the Astros from 1997 to 2009. He moved to the front office as a special assistant to the general manager for five years before being assigned as a Community Outreach Executive.^[13] In 2005, he agreed to coach for the team representing Puerto Rico in the 2006 World Baseball Classic, which was managed by José Oquendo, and included his own son, José Cruz, Jr.

Jose Cruz was inducted into the Hispanic Heritage Baseball Museum Hall of Fame on September 13, 2002 in a on-field ceremony (done prior to a game) at Minute Maid Park in Houston. He was inducted into as part of the inaugural class of the Astros Hall of Fame in August 2019.