The Philadelphia Phillies selected Singleton in the eighth round of the 2009 MLB Draft. He had been projected for selection as high as the second round of the draft, but his senior year statistics caused him to fall a few rounds. Singleton reported to the Gulf Coast League Phillies, where he played 31 minor league games that year. He spent 2010 with the Class ALakewood BlueClaws, where he hit for a.290 batting average, 14 home runs and 77 runs batted in. Prior to the 2011 season, Singleton was considered the Phillies' second best prospect by Baseball America.
Houston Astros
On July 29, 2011, the Phillies traded Singleton, Jarred Cosart, Josh Zeid, and Domingo Santana to the Houston Astros in exchange for Hunter Pence. Baseball America designated Singleton as Houston's top prospect following the 2011 season. He was named to appear in the 2012 All-Star Futures Game. Singleton tested positive for marijuana in June 2012. He competed in the Arizona Fall League that offseason, and had a second positive test for marijuana in December. On January 9, 2013, Singleton was suspended for 50 games due to his second failed drug test. Singleton said that he had grown up around friends who used the drug and that he had been using it "on and off" since he was 14 years old. He spent a month in a rehabilitation center after the second failed test. Following the 2013 season, the Astros added Singleton to their 40 man roster. On June 2, 2014, the Astros signed Singleton to a 5-year contract that guaranteed him $10 million, and could have been worth as much as $35 million. The extension was the first to be signed by a drafted player with no major league experience. Singleton was promoted from the Oklahoma City RedHawks of the Class AAAPacific Coast League to make his major league debut on June 3. Singleton made his major league debut for the Astros on June 3, 2014 against the Los Angeles Angels of Anaheim. In his first game, he went 1–3 with a home run, 2 RBI's, a walk, and two strikeouts. His first home run, a solo home run, was off of Matt Shoemaker. On June 8, Singleton lined his first career grand slam off of Glen Perkins of the Minnesota Twins at Target Field to help the Astros to a 14–5 win. Teammates Dexter Fowler, Chris Carter, and George Springer also homered. On August 2, 2014, Singleton hit an Inside-the-park home run against the Toronto Blue Jays. It was initially ruled an out by the home plate umpire, but was later reversed following a challenge by Astros manager Bo Porter. The Astros optioned Singleton to the Fresno Grizzlies of the PCL to start the 2015 season. On May 13, 2015, Singleton recorded 10 RBIs, including a grand slam and two-run home run. His 10 RBIs was one short of the modern day PCL record. Singleton had 22 RBI in a five-day span, including 18 in Fresno's four game series in Albuquerque from May 12–15, which included two grand slams. On November 19, 2016, Singleton was placed on outright waivers by the Astros. He cleared waivers on November 22 and was assigned to Fresno. He played the 2017 season with the Corpus Christi Hooks of the Class AATexas League, and led all minor leaguers with 500 or more plate appearances with a walk percentage of 26.4%. On May 21, 2018, he was released by the organization while serving a 100 game suspension in the final year of his contract.
Diablos Rojos del México
On April 2, 2020, Singleton signed with the Diablos Rojos del México of the Mexican League.
