Guyer helped Herndon break a six-year Northern Region playoff drought, leading the Hornets to a 7–4 season.

[5] After the 2010 season, the Cubs traded Guyer, Hak-ju Lee, Chris Archer, Robinson Chirinos, and Sam Fuld to the Tampa Bay Rays for Matt Garza, Fernando Perez, and Zac Rosscup.

The next day, in his first major league at bat, he hit a two-run home run off of Baltimore Orioles rookie pitcher Zack Britton.

[10] Guyer began the 2012 season with Triple-A Durham, hitting .294 with three home runs and 13 RBIs in 22 games before being recalled to Tampa Bay on May 9 after Jeff Keppinger was placed on the restricted list.

[11] Guyer played in three games with Tampa Bay, going 1–for-7 with a home run, before he hit the disabled list with a shoulder strain.

[12] On May 25, the Rays announced that Guyer was placed on the injured reserve list after undergoing surgery to repair a torn labrum in his left shoulder.

[15] The MLB single-game record for being hit by pitches is three, and Guyer has been the recipient twice: on October 2, 2015, vs. the Mets, and on April 21, 2016, vs. the Red Sox.

"[1] On August 1, 2016, the Rays traded Guyer to the Cleveland Indians in exchange for prospects Nathan Lukes and Jhonleider Salinas.

[25] Guyer was included as a defendant in a $5 million lawsuit filed in April 2012 with fellow Rays prospect, Matt Bush.