He played in Major League Baseball (MLB) for the Toronto Blue Jays, Houston Astros and Chicago Cubs.

[2] He was demoted to the Short Season-A Salem-Keizer Volcanoes in June, where he made 14 appearances (12 starts) and pitched to a 2–4 record, 4.27 ERA, and 63 strikeouts in 59 innings.

[2] In 2014, Biagini was promoted to the Advanced-A San Jose Giants, and made 23 starts for the team, finishing the year with a 10–9 record, 4.01 ERA, and 103 strikeouts in 128 innings pitched.

[2] He would play the entire 2015 season with the Double-A Richmond Flying Squirrels and threw a career-high 1301⁄3 innings over 23 appearances (22 starts).

[5] On March 30, 2016, manager John Gibbons announced that Biagini had made the Opening Day roster, and would pitch out of the bullpen.

[6] He made his Major League debut on April 8, pitching a perfect 9th inning against the Boston Red Sox, and struck out David Ortiz for his first career strikeout.

[9] Biagini did not yield a home run until September 3, when Kevin Kiermaier of the Tampa Bay Rays hit a two-run shot in a 7–5 loss for the Blue Jays.

[15] He returned to the major leagues, and the rotation, on August 27, allowing 5 runs over 32⁄3 innings in a 7–2 loss to the Minnesota Twins.

[16] On September 1, in a game against the Baltimore Orioles, Biagini had his best start as a Blue Jay to date, throwing 7 shutout innings and striking out a career-high 10 batters, though Toronto would eventually lose 1–0 in the 13th.

[18] The Blue Jays called up Biagini to make a spot start on April 17, for the second game of their doubleheader against the Kansas City Royals.

[20] On July 31, 2019, Biagini was traded to the Houston Astros (along with Aaron Sanchez and Cal Stevenson) in exchange for Derek Fisher.