[1][3] Luzardo had torn his ulnar collateral ligament in his pitching arm and had undergone Tommy John surgery, performed by Dr. James Andrews, in March 2016.

The Nationals, who drafted him in the third round, were known for taking chances on players who had already undergone or needed to have Tommy John surgery, and committed to completing his rehabilitation.

[5] The Nationals traded Luzardo, Sheldon Neuse, and Blake Treinen to the Oakland Athletics on July 16, 2017, for Sean Doolittle and Ryan Madson.

A strained left rotator cuff late in spring training resulted in him being shut down and missing the start of the season.

[12] On June 11, 2019, Luzardo returned to the mound with Class A-Advanced Stockton, and allowed one run over seven innings spanning two outings with 11 strikeouts before being promoted to the Triple A Las Vegas Aviators.

The diagnosis forced the A's to put Luzardo in the bullpen to begin the season, but he only needed two relief appearances before making his first big league start on August 4 against the Texas Rangers.

Luzardo began the 2021 season in the A's rotation, but struggled to a 5.79 ERA over six starts before requiring time on the injured list, after accidentally slamming his throwing hand on a table while playing a video game, resulting in a fractured pinky.

[20] He began his tenure with four scoreless innings, but allowed six home runs in his next five outings before being optioned to Triple-A Las Vegas on June 21.

[30] On December 22, 2024, the Marlins traded Luzardo and Paul McIntosh to the Philadelphia Phillies in exchange for prospects Starlyn Caba and Emaarion Boyd.

At approximately 2:20 P.M., a former student opened fire at the school—before Luzardo had arrived, he received a text from his former coach advising him not to come to the school.