Difo signed with the Washington Nationals as an international free agent on June 3, 2010. He made his professional debut that season for the Dominican Summer League Nationals. From 2010 to 2013, he played for the Gulf Coast Nationals, Auburn Doubledays, Hagerstown Suns and Potomac Nationals. Difo played the 2014 season with Hagerstown. He was named the 2014 South Atlantic LeagueMost Valuable Player with a.315 batting average, a.360 on-base percentage and a.470 slugging average, with 14 home runs and 90 runs batted in. He received the Bob Boone Award from the Nationals, which "recognizes professionalism and passion". Difo started 2015 with the Potomac Nationals and was promoted to the Double-A Harrisburg Senators after 19 games. On May 19, 2015, Difo was called up to the major leagues for the first time and collected his first hit in his first at-bat the same day, a pinch-hit single up the middle off New York Yankees reliever — and future Nationals teammate — David Carpenter. Difo hit his first career home run on September 29, 2016, off Arizona Diamondbacks starter and former Nationals pitching prospect Robbie Ray. On October 14, 2016, he struck out for the game's last out as a pinch hitter as the Los Angeles Dodgers defeated the Washington Nationals 4-3 to win the National League Division Series. Difo received his first career start in the outfield on June 24, 2017, playing center field against the Cincinnati Reds due to an injury to regular center fielder Michael A. Taylor. After Trea Turner suffered a broken wrist in a game days later, Difo took over as the Nationals' regular starting shortstop, occasionally sharing duties with Stephen Drew and Adrián Sánchez. On July 27, 2017, Difo hit one of four consecutive home runs by Nationals hitters off Milwaukee Brewers starter Michael Blazek, the first time the feat had been accomplished in Major League Baseball since the 2011 season. Splitting time between the Majors and Minors in 2019, Difo appeared in 43 games with the Nationals and had a.252 average with 2 home runs and 8 RBI. The Nationals finished the year with a 93-69 record, able to clinch a wild card spot. Difo did not seek any postseason action, but was still on the Nationals' 40-man roster at the time when the team went on to win the 2019 World Series over the Astros, their first championship in franchise history.
Personal
During the 2017 season, Difo attracted some media attention for his choice of walk-up music, as he frequently had romantic ballads like "Unchained Melody" and "My Girl" added to his rotation. Although some of Difo's teammates told The Washington Post they assumed someone was playing a joke on the young infielder, Difo explained to the paper, "I love those songs." Difo chose to go by the nickname El Lindo, Spanish for "the beautiful one", for MLB Players' Weekend in 2017. The nickname was reportedly given to him by Nationals teammate Adam Lind.
