The 'Young Adult' actress has been chosen to front one of the last episodes of the hit NBC show's most recent series on May 10.
She will put her comedic talents to the test when she makes her hugely-anticipated appearance to promote her new Seth MacFarlane western, 'A Million Ways to Die', E! Online reports.
Joining the 38-year-old star in the recently announced line-up are 'The Amazing Spider-Man' favourite Andrew Garfield, and Lonely Island joker and 'SNL' regular Andy Samberg, who are hosting on May 3 and May 17 respectively.
Charlize will be joined by indie rockers The Black Keys, who have already performed on the show twice, while Andrew's episode will feature a live set from Coldplay and Andy will be accompanied by first-time performers St. Vincent.
Meanwhile, Charlize's romance with Sean Penn has allegedly been heating up. The actor is said to be seriously smitten with the screen beauty and is expected to propose in the near future.
The pair have been inseparable since they started dating late last year and went public with their relationship at Sean's third annual Help Haiti Home gala in January.