[3] He played baseball in San Carlos Little League[4] and went to Saint Francis High School in Mountain View, California.

He made the West Catholic Athletic League first teams in each of last two seasons, including WCAL MVP distinction in 2004.

He also played football, winning first-team All-WCAL, second-team All-CCS and honorable mention All-Metro as a senior.

[10] Following the draft, Descalso began his professional career with the Batavia Muckdogs, the Short-Season A affiliate of the Cardinals in the New York–Penn League.

However, he did not play in that game, instead was promoted to Triple-A Memphis in early July when Jarrett Hoffpauir was recalled by the Cardinals.

He missed final two weeks of 2009 season to play for the gold medal winning team USA in the 2009 Baseball World Cup in Italy.

[13] He officially made his major league debut on September 18, 2010, at home against the San Diego Padres when he was announced as a pinch hitter (although he did not bat and was replaced by right-handed batter Nick Stavinoha).

[14] His first game as a starter was on September 22, 2010, against the Pirates at their park, where he garnered his first hit and first RBI with a two-run double.

However, the Cards had a number of capable infielders fighting for roster spots, including David Freese, Tyler Greene, Double-A prospect Matt Carpenter, and off-season acquisitions Ryan Theriot and Nick Punto.

An injury to Punto[16] and questions about Freese's durability left the Cards desperate for an extra utility infielder rather than an outfielder.

[21] On May 21, 2013, Decalso hit his first career grand slam and tallied a career-high five runs batted in as the Cardinals beat the San Diego Padres 10–2 at Petco Park.

[23] Descalso made his major league pitching debut against the Chicago Cubs in the top of the ninth inning with two outs on May 12, 2014.

Descalso began the 2016 season on the disabled list with a broken hand suffered in spring training.

[30] In 2016, Descalso appeared in 99 games, bouncing back offensively by hitting .264 with a career-high eight home runs and 38 RBI.

Descalso served as a veteran presence on the Rockies,[31] while also filling an important utility role, receiving time at six different positions over the course of his two seasons at Colorado.

On February 7, 2017, Descalso signed a one-year, $1.5 million deal with the Arizona Diamondbacks with an option for 2018, and entered a heated competition for a bench spot on Opening Day.

[36] On May 13, 2021, Descalso signed a minor league contract with the Minnesota Twins organization and was assigned to the Triple-A St. Paul Saints.