[4] He played the entire 2006 minor league season with the Rookie-Advanced Kingsport Mets, appearing in 36 games and batting .235 with one home run and 12 RBI.

[4] In the offseason, Thole played in 19 games for the Peoria Saguaros of the Arizona Fall League, where he was named a Rising Star,[5] batting .319 with two home runs and 17 RBI.

[4] He was assigned to the Double-A Binghamton Mets to open the 2009 season, and hit .328 with one home run and 46 RBI in 103 games.

[7] During the offseason, Thole played in 44 games for the Leones del Caracas of the Venezuelan Winter League, and hit .381 with three home runs and 28 RBI.

[8] On July 20, 2010, Thole hit his first major league home run, a solo homer, off of Barry Enright in a game against the Arizona Diamondbacks at Chase Field.

On May 9, 2012, Thole was placed on the seven-day disabled list after suffering a concussion in a plate collision with Phillies first baseman Ty Wigginton on May 7.

On December 17, 2012, the Mets traded Thole, R. A. Dickey, and Mike Nickeas to the Toronto Blue Jays in exchange for Travis d'Arnaud, Noah Syndergaard, John Buck, and Wuilmer Becerra.

[13] On March 24, Thole was reassigned to minor league camp and started the season with the Triple-A Buffalo Bisons.

[16] After the signing of Russell Martin in the offseason, the Blue Jays entered 2015 spring training with three catchers on their roster.

He hit his first home run of the season on April 5, in the Blue Jays 5–3 win over the Tampa Bay Rays.

[23] After the Blue Jays reacquired Dioner Navarro from the Chicago White Sox on August 26, Thole's role with the team was brought into question.

After catching Dickey's start on August 28, Thole was designated for assignment by Toronto, who hoped that he would go unclaimed off waivers and be released, and could be re-signed on September 1 after the Major League roster expansion.

On March 18, Diamondbacks manager Torey Lovullo stated that Thole would likely require surgery and miss the entire 2017 season.