He started his baseball career in the early 2000s for the Venezuelan Summer League and even had a breakthrough time in 2007. The next year he moved to the United States, playing for the Greeneville Astros in the Rookie-level Appalachian League. He returned to Greeneville in 2009 and hit  a .324 batting average with 21 stolen bases in just an amazing 45 games, rightfully earning him a spot on the leagues All Star team, while also receiving team MVP honors for his performance.

Afterwards, still in the minor league, he joined the Lexington Legends of the Class A South Atlantic League in 2010, hitting a .308 batting average with 39 steals and surprisingly 11 home runs and again earning a spot on the league all star team. In the same year he also played for the Lancaster JetHawks in the Class A California League and hit a batting average of .276. The next year he became apart of the Corpus Christi Hooks team of the Class AA of the Texas League where he hit a  .361 batting average, giving him overall stats of .389 batting average with 26 walks, 24 steals, and 40 strike outs in 357 minor league at-bats that year. Following his impressive minor league performance, Jose Altruve was named the second baseman on Baseball America's 2011 Minor League All Star Team and he also received the Houston Astros Minor League Player of the Year award.

In July 19, 2011, he finally moved to the major league by playing for the Houston Astros. Upon making his MLB debut, he was originally listed at the height of 5'7", but he has since been correctly listed at his real height, and became the second shortest player to ever play in the major leagues, standing 5'6", and the shortest since Freddie Patek retired following the 1981 season. He had a batting average of  .346 over his first 21 games before having a run of bad games, and ended the year with a .276 batting average.

He also hit two home runs, stole seven bases, and delivered a .358 slugging average in 221 at-bats. At first Jose represented his team during the 2011 All-Star Futures Game. At the end of the year he returned to his native Venezuela and was involved in the Navegantes del Magallanes team in the Venezuelan Winter League. In 2013 he signed a four year contract with the Astros and $12.5 million dollar extension. 2014 was even more successful than previously, and in June, during the match against the Detroit Tigers team he stole two bases.

He had 130 hits and 40 stolen bases before the All-Star Break and became the 1st MLB player since 1933, who did it. In the same year he appeared in Japan with participation in the 2014 Major League Baseball Japan All-Star Series. In the last game of the 2015 season, Jose went 3 for 5 to hit the 2 hundred hit mark for the 2nd season in a row. He became the first player in Houston Astros team history to achieve two 200 hit seasons in line. Being a Venezuelan, he also is the first player from his country who did a multiple 200 hits seasons. Jose has had an incredible career in the MLB, leading the American League in stolen bases and becoming the first Astro ever to win a batting title by hitting .341. He won two more AL batting titles in 2016 and 2017 and helped the Astros win a World Series title in 2017.