He played in Major League Baseball (MLB) for the Chicago Cubs, San Diego Padres, Miami Marlins, Texas Rangers, Baltimore Orioles, and Boston Red Sox.

The second of three children, he grew up on a 15-acre (6.1 ha) ranch where he became an expert at horseback riding and calf roping, and was involved in the local 4-H and Future Farmers of America youth organizations.

On January 6, 2012, the San Diego Padres acquired Cashner and outfielder Kyung-Min Na from the Cubs for first baseman Anthony Rizzo and right-handed starting pitcher Zach Cates.

[14] The injury delayed Cashner's preparation for 2013,[15] but by the end of April he was part of the Padres' starting rotation after beginning the season in the bullpen.

[16] On July 27, 2013, Cashner hit his first career home run off of Arizona Diamondbacks pitcher Josh Collmenter.

On September 16, Cashner pitched a one-hit complete-game shutout against the Pittsburgh Pirates in which he faced the minimum 27 batters.

He missed about three months of the season with elbow, shoulder, and neck injuries and was winless for 11 straight starts despite a 2.86 ERA in that stretch.

On April 24, Cashner played left field for one at bat after Seth Smith suffered an injury in an extra inning game versus the Washington Nationals.

On July 29, 2016, the Padres traded Cashner, Colin Rea, and Tayron Guerrero to the Miami Marlins for Jarred Cosart, Carter Capps, Josh Naylor, and Luis Castillo.

[24] On February 15, 2018, Cashner signed a two-year, $16 million contract with the Baltimore Orioles that also contained a vesting option for a third year.

[26] In the first year of his two-year contract, Cashner dealt with a couple of DL stints, finishing the season with a 4–15 record in 28 starts; he struck out 99 in 153 innings.

On July 13, 2019, Cashner, along with cash considerations, was traded to the Boston Red Sox in exchange for minor league position players Noelberth Romero and Elio Prado.

Padres catcher René Rivera said Cashner that season "learned how to be a pitcher" who can "get outs quick", as opposed to being a mere thrower.

The foundation grew out of their experience watching their mother survive breast cancer in 2004 and then lose a leg after suffering septic shock in 2015.