Following his high school career, the San Diego Padres selected Eflin in the first round, with the 33rd overall selection, of the 2012 MLB draft. Rather than enroll at UCF, Eflin signed with the Padres, receiving a $1.2 million signing bonus. Eflin began his professional career in 2012 with the AZL Padres in the Arizona League, with a record of 0–1 with a 7.71 ERA in seven innings. His performance was hampered by mononucleosis. He pitched for the Fort Wayne TinCaps of the Class AMidwest League in 2013. Eflin was 7–6, and his 2.73 ERA led the league, as he had 86 strikeouts in 118.2 innings. In 2014, Eflin pitched for the Lake Elsinore Storm of the Class A-AdvancedCalifornia League, and he finished the season with a 10–7 win–loss record and a 3.80 ERA, with 93 strikeouts in 128 innings.
Philadelphia Phillies
On December 18, 2014, the Padres traded Eflin, Joe Wieland, and Yasmani Grandal to the Los Angeles Dodgers in exchange for Tim Federowicz, Matt Kemp, and cash. The Dodgers then traded Eflin, along with Tom Windle, to the Philadelphia Phillies for Jimmy Rollins. Baseball America named him the 4th-best prospect in the Phillies minor league system prior to the 2015 season. The Phillies invited Eflin to spring training as a non-roster player. Eflin spent the 2015 season with the Reading Fightin Phils of the Class AAEastern League, and pitched to an 8–6 record with a 3.69 ERA and a 1.21 WHIP, with 68 strikeouts in 131.2 innings. He was the April 12 Eastern League Pitcher of the Week, and a mid-season Eastern League All Star. He pitched for Team USA in the 2015 Pan American Games, which won the silver medal. Eflin received another invitation to spring training in 2016. Eflin began the 2016 season with the Lehigh Valley IronPigs of the Class AAAInternational League, and was named the league's Pitcher of the Week on April 18. With Lehigh Valley, he was 5–2 with a 2.90 ERA and 55 strikeouts in 68.1 innings. Eflin made his MLB debut on June 14, 2016, at 22 years of age, allowing eight earned runs by the Toronto Blue Jays in innings on nine hits, three of which were home runs. Eflin's game score of five was the sixth-worst debut in major league history, and worst in Phillies franchise history. Eflin rebounded with two complete games in the month of July, including a Madduxshutout of the Atlanta Braves. The Phillies placed Eflin on the disabled list on August 9 due to patellar tendinopathy in both knees, and he underwent season-ending knee surgery ten days later. In 2016 with the Phillies, he was 3–5 with a 5.54 ERA, and 31 strikeouts in 63.1 innings. Eflin began the 2017 season on the 10-day disabled list in an effort to continue recovery from both knees. He was activated on April 11 and optioned to Triple-A. He was the April 17, 2017 International League Pitcher of the Week. On April 18, he was recalled by the Phillies to replace Clay Buchholz in the rotation. His season debut was the same night against the New York Mets. In 2017 with the Phillies, he was 1–5 with a 6.16 ERA, and 35 strikeouts in 64.1 innings. That season with Lehigh Valley, Clearwater, and the GCL Phillies he was 2–4 with a 3.74 ERA and 50 strikeouts in 55.1 innings. In 2018 with the Phillies, Eflin was 11–8 with a 4.36 ERA, and 123 strikeouts in 128 innings. With Lehigh Valley, he was 2–2 with a 4.05 ERA and 15 strikeouts in 20 innings. For the 2019 season, Eflin began the season in the rotation before being placed on the disabled list on May 31 with a back injury. In 2019 with the Phillies, Eflin was 10-13 with a 4.13 ERA, as in 32 games he pitched two complete games and one shutout over 163.1 innings in which he gave up 28 home runs.
