The Lupita Nyong'o-starring psychological horror scored the highest grossing opening weekend for an original horror, generating $70 million (£53 million).
The record was previously held by A Quiet Place, which debuted to $50.2 million (£38 million) at the US box-office.
Us has also scored the second-highest grossing opening ever for an original R-Rated film, only behind the Seth MacFarlane comedy Ted.
Only Captain Marvel has had a bigger opening weekend this year, with the superhero blockbuster scoring a $153 million (£116 million) weekend earlier this year.
“Put simply, Jordan Peele is a genius,” Jim Orr, Universal’s president of domestic distribution, told Variety. “He’s managed to tap into something that the domestic box office can’t get enough of. People can’t wait to see what he does next.”
Peele's last film, Get Out, also surpassed box-office expectations. Made on a production budget of $4 million ($3 million), the 2017 film launched with $33 million ($25 million) and went on to make $255 million (£193 million) worldwide. Us has so-far made $86.95 million (£65.88 million) worldwide.