The theoretical physicist is said to have filmed scenes for the CBS sitcom's episode on April 5.
According to TV Guide Canada, Hawking's cameo sees him have a "run-in" with Sheldon (Jim Parsons).
The 70-year-old cosmologist has been approached to appear on The Big Bang Theory in the past, but he was said to be too ill to film.
He has previously starred in The Simpsons, Futurama and Star Trek: The Next Generation.
Leonard Nimoy is set to feature in the episode prior to Hawking's as his Star Trek character Spock.
The Big Bang Theory airs Thursdays, 8/7c on CBS.