The Fox pilot - retitled Friends & Family - will star Jason Ritter (Parenthood) and Alexis Bledel (Gilmore Girls) as the two leads.
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Kaczmarek will play Pam, the overbearing mother of Ritter's character Gavin, TVLine reports.
The 57-year-old actress is best known for playing another overbearing mother - Lois on Fox sitcom Malcolm in the Middle, which ran from 2000 to 2006 on Fox.
Also cast in Friends & Family is Dustin Ybarra, who was previously linked to a US remake of BBC sitcom Only Fools and Horses.
James Corden and Ruth Jones - who co-created the original Gavin & Stacey and also starred in the series - will serve as executive producers on the US remake.
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Watch a clip from the original Gavin & Stacey below:
