The actress - best known for playing Chloe O'Brian on the Fox drama - will appear in the penultimate episode of season eight, TVLine reports.
Rajskub and Lost actor Patrick Fischler will play a married couple who develop a mysterious illness in the episode, titled 'Migration'.
In addition to her 24 role, Rajskub has appeared on ABC's Modern Family and short-lived CBS sitcom How to Be a Gentleman.
Her Grey's Anatomy appearance will air on May 10, with the show's eighth season finale transmitting the following Thursday, May 17.
Grey's Anatomy star Sarah Drew (Dr April Kepner) recently hinted that the finale will contain a "super-dramatic cliffhanger" and described the instalment as "huge", "sad" and "intense".
The series continues tonight at 9/8c on ABC and airs on Wednesdays at 10pm on Sky Living in the UK.