Beginning in 2019, he landed in the major leagues and became an anchor of the Phillies' starting rotation in 2019–21 seasons, but a right knee contusion resulted in a stint on the 60-day injured list, and Eflin was moved to the bullpen after his return in September 2022.

While he was in high school, he grew seven inches and became a dominant starting pitcher who attracted attention from colleges and professional scouts.

[7] Eflin began his professional career in 2012 with the AZL Padres in the Arizona Fall League, with a win–loss record of 0–1 and a 7.71 ERA in seven innings.

[10] After his first season, scouts thought that he had a good chance to have a strong career in the major leagues, but injury concerns had already begun to mount.

[13][14] In 2014, Eflin pitched for the Lake Elsinore Storm of the High–A California League, and he finished the season with a 10–7 win–loss record and a 3.80 ERA, with 93 strikeouts in 128 innings.

[15][9] After the season, he was ranked the number five prospect in the Padres' system, recognized by scouts for his "stellar control" who avoided issuing walks to opposing hitters.

[16] On December 18, 2014, the Padres traded Eflin, Joe Wieland, and Yasmani Grandal to the Los Angeles Dodgers in exchange for all-star outfielder Matt Kemp, Tim Federowicz, and cash.

"[19] During spring training in 2021, Eflin—the last player acquired during Amaro's 2015 rebuilding efforts still to be in the Phillies organization—reflected on the trade as a turning point for his career, noting that the moment made it feel "like someone wanted me more.

[24][25] Eflin has said of Knapp, "Sometimes, I feel like he knows me better than myself ... A great thing about Knappy is he cares a lot more about the pitch calling and defensive catching than he does hitting.

[37] His season debut was the same night against the New York Mets, and he began a 29-inning streak of not allowing any runs to opposing hitters that spanned four starts.

[23][30] That season—his time split between Lehigh Valley, the Class A-Advanced Clearwater Threshers, and the GCL Phillies—he combined to go 2–4 with a 3.74 ERA and 50 strikeouts in 55+1⁄3 minor league innings.

Although the approach initially showed signs of success, leading to speculation he could be an all-star candidate, he eventually began to struggle before suffering an injury midway through the season and losing his spot in the Phillies' starting rotation.

[41][42] He ultimately made 11 starts in 2020, and the Phillies won eight of them; he also posted a career-best 10.9 strikeouts per nine innings to accompany a 3.97 ERA and 4–2 record.

On November 7, 2022, two days after Phillies lost the 2022 World Series, Eflin declined his end of the mutual option for 2023 season, and became a free agent for the first time in his career, receiving a $150,000 buyout.

This was the largest free agent deal in Rays history, topping the five-year, $35 million contract given to Wilson Álvarez before their inaugural 1998 season.

[49] Eflin was reportedly offered the exact same contract terms by the division-rival Boston Red Sox, but declined, citing his Orlando roots and the opportunity to work with Rays pitching coach Kyle Snyder.

[51] On July 26, 2024, Eflin was traded with cash considerations to the Baltimore Orioles in exchange for Matthew Etzel, Jackson Baumeister, and Mac Horvath.

[52] He won his Orioles debut in an 11–5 home victory over the Toronto Blue Jays three days later in the first game of a twi-night doubleheader on July 29.

He completed six innings, struck out seven without a walk and gave up ten hits which included an Addison Barger one-out, three-run homer in the fifth.

[54] He joined Jack Harshman as the second Orioles pitcher to win each of his first five appearances with the ballclub in a 6–1 away victory over the Colorado Rockies after being activated twelve days later on September 1.