Texas Rangers

Castillo began his professional career as a starting pitcher in 2006, playing for the Dominican Summer Rangers and AZL Rangers, going a combined 1–4 with a 3.10 ERA in eight games (seven starts). That year, he struck out 41 batters in 29 innings. In 2007, Castillo went 3–5 with a 5.92 ERA in 14 starts for the Spokane Indians, allowing 73 hits in 62 1/3 innings.^[1]

He converted to relief pitching in 2008, going 2–5 with a 5.28 ERA in 36 games (seven starts) for the Clinton LumberKings. In 2009, he went 3–6 with a 4.05 ERA in 40 games (two starts) for the Hickory Crawdads. He split 2010 between the Bakersfield Blaze and Frisco RoughRiders, going a combined 1–3 with a 2.11 ERA in 39 relief appearances. He struck out 67 batters in 55 1/3 innings. In 2011, he was 3–6 with a 6.36 ERA in 42 games for Frisco and in 2012, he was 4–1 with a 3.54 ERA in 35 games for Frisco and the Round Rock Express.

San Francisco Giants

He pitched in the San Francisco Giants system in 2013 and went 6–7 with a 5.34 ERA in 37 games between the Richmond Flying Squirrels and Fresno Grizzlies.

Baltimore Orioles/Cincinnati Reds

In 2014, he latched on with the Baltimore Orioles—and later pitched in the Cincinnati Reds system—and went 2–2 with a 3.84 ERA in 40 games between the Bowie Baysox, Pensacola Blue Wahoos and Triple-A Louisville Bats.^[1]

Vaqueros Laguna

He began 2015 with the Vaqueros Laguna in the Mexican League and had a 3.55 ERA in 30 games with the club.^[1]

Hanwha Eagles

Castillo signed with the Hanwha Eagles of the KBO League for the 2016 season. On June 25, 2016, he made his KBO debut.^[1]

Los Angeles Dodgers

Castillo signed with the Los Angeles Dodgers for the 2017 season and was assigned to the Triple-A Oklahoma City Dodgers.^[2] He was added to the 40-man roster on June 8 but remained in Oklahoma City.^[3] In 22 appearances (16 starts) for Oklahoma City he was 4–8 with a 4.27 ERA.^[1]

Castillo was called up to the majors by the Dodgers on September 1, 2017.^[4] He made his major league debut the following night against the San Diego Padres, pitching 1+1⁄3 innings without allowing a run. He struck out two batters, including the first batter he faced, Jabari Blash.^[5] He was designated for assignment on September 6 after appearing in just two games, the second of which he allowed two runs to score without recording an out.^[6][7] He elected free agency following the season on November 6, 2017.^[8]

Saitama Seibu Lions

Castillo signed with the Saitama Seibu Lions of Nippon Professional Baseball. The Lions released him on August 7, 2019.^[9]