The sitcom, now titled Susan 313, will star Silverman as a woman readjusting to being single after a decade spent in a relationship.
Goldblum will play her ex-boyfriend, according to Vulture.
The 59-year-old actor is best known for his film roles including 1986's The Fly, 1993's Jurassic Park and 1996's Independence Day.
His television credits include a starring role on Law & Order: Criminal Intent and a recent stint on Glee.
Lost star Ken Leung will also appear in Susan 313 as a new love interest for Silverman's character. Parks and Recreation's Harris Wittels and Party Down actress June Diane Raphael make up the remainder of the lead cast.
The project landed at NBC in August after reportedly sparking a bidding war between television networks.
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