Urshela signed with the Cleveland Indians as an international free agent in July 2008. He made his professional debut in 2009, playing for the Dominican Summer League Indians and the Arizona League Indians.

Before the 2013 season he played for the Colombian national baseball team in the qualifiers for the World Baseball Classic, but the team lost to Panama and failed to qualify for the tournament. He played for the Colombian national baseball team again after they qualified for the 2017 World Baseball Classic.

Urshela started the 2014 season with Akron and was promoted to the Columbus Clippers of the Class AAA International League during the season. After the 2014 season, the Indians added Urshela to their 40-man roster. He was named the Indians’ fourth best prospect by MLB.com in 2015.

Urshela began the 2015 season with Columbus. He was called up to the major leagues on June 8, 2015. He got his first major league hit, a single, and first major league home run in the same game against the Seattle Mariners on June 11, 2015. He spent the entie 2016 season playing with Columbus and in the offseason he played winter baseball in the Venezuelan Professional Baseball League for Águilas del Zulia alongside future Yankees teammate Mike Tauchman.

He batted .224 in 67 major league games for Cleveland in 2017.

On May 9, 2018, Cleveland traded Urshela to the Toronto Blue Jays for cash considerations or a player to be named later. Urshela batted .233 with one home run and three RBIs in 19 games for Toronto, before he was designated for assignment by the Blue Jays on June 26. He cleared waivers and was assigned outright to the Triple-A Buffalo Bisons on July 3. He batted .244 in 91 plate appearances for the Bisons.

On August 4, 2018, the Blue Jays traded Urshela to the New York Yankees in exchange for cash considerations. The Yankees assigned him to the Scranton/Wilkes-Barre RailRiders. He worked with Phil Plantier, the RailRiders’ hitting coach, to make changes to his batting stance. Urshela batted .307 in 107 plate appearances for Scranton/Wilkes-Barre.

The Yankees selected Urshela’s contract on April 6, 2019, after Miguel Andújar, the Yankees’ starting third baseman tore his right shoulder labrum. Urshela began the season hitting 25-for-71 (.352), and continued to play for the Yankees when Andújar returned briefly in May, though Andújar soon opted to have season-ending surgery.

Urshela opened the 2020 season as the Yankees starting 3rd baseman, he played in 43 of the teams 60 games missing time with a groin injury in late August. On September 30, 2020 Urshela became the first Yankees third baseman to hit a post-season grand slam doing so against his former team, the Cleveland Indians. This also helped the Yankees sweep the Indians in the Wild Card Series, winning 2 games out of a best-of-3.