Ultimately, Smith became Wright State's closer during his junior and senior years, as he gained 4–6 miles per hour (6.4–9.7 km/h) on his fastball after changing his delivery.

In 2005, Smith briefly pitched for the Rockville Express, a team in the Cal Ripken, Sr. Collegiate Baseball League.

In 16 regular-season appearances, totaling 17+1⁄3 innings pitched, he tallied nine saves with a 2.08 ERA, a .197 batting average against, and struck out 19 batters.

He also recorded the final out of the 2005 Petitt Cup tournament, on a comebacker, to give Edenton its second consecutive league championship.

When Duaner Sánchez was hurt during a taxi cab incident in 2006, Mets general manager Omar Minaya considered recalling Smith to the major leagues.

Instead, the Mets traded for Roberto Hernández and Óliver Pérez to give Smith more time in the minors[citation needed].

On December 10, 2008, Smith was traded by the Mets to the Cleveland Indians as part of a twelve-player, three-team deal.

[3] On January 18, 2013, the Cleveland Indians announced they had avoided arbitration with Smith, signing him to a one-year contract worth $3.15 million.

After the Angels traded for San Diego Padres' All-Star closer Huston Street on July 18, 2014, Smith was moved to an eighth-inning setup role.

[10][11] Smith became the Blue Jays setup man early in the season, after Jason Grilli struggled in the role and Joe Biagini was moved to the starting rotation.

On July 31, 2017, the Blue Jays traded Smith to the Cleveland Indians for Thomas Pannone and Samad Taylor.

[18] Smith did not play in the abbreviated 60-game 2020 season and forfeited his $4M salary after returning to Ohio to spend time with his mother who was battling the final stages of Huntington's disease.

[20] On July 27, 2021, Smith was traded to the Seattle Mariners along with Abraham Toro in exchange for Rafael Montero and Kendall Graveman.

[28] In 2012, Smith's mother was diagnosed with Huntington's disease; the condition leads to the death of nerve cells in the brain.

[27] Smith and LaForce dedicate much of their free time to raising awareness for their organization HelpCureHD.org, which provides funding for couples to go through the PGD-IVF process as a way to stop the disease from continuing to future generations.