The former Vampire Diaries star will play a love interest for Dean (Jensen Ackles), according to TVLine.
Her character Lydia will appear in the 13th episode of the show's current season, expected to air in late January.
"[Lydia is] wry, independent, and as fun-loving as Dean." said showrunner Sera Gamble. "[They] have a memorable evening that takes an unexpected turn."
Canning starred as Jenna Sommers on fellow CW drama The Vampire Diaries and also played a recurring role on Smallville in 2008.
Jason Dohring has also signed up for a guest stint on Supernatural.
The Ringer actor will play the god of time Chronos in the 12th episode of the season.
The Supernatural midseason finale airs on Friday at 9/8c on The CW.
> Supernatural: 'How to Win Friends and Influence Monsters' recap
Watch a preview of this week's Supernatural below: