The Disney and Marvel film, starring Benedict Cumberbatch, took $43m (£34.3m) between Friday and Sunday.
Disney has already secured its best year on record at the global box office, which now tops $6bn (£4.7bn).
It has set a domestic box office annual record of $2.3bn (£1.8bn), beating last year's high of $2.27bn (£1.81bn).
In second position, Fox and Dreamworks' Trolls took an estimated $35m (£27.9m), only dropping by 24.8% in its second week.
Arrival, a sci-fi drama starring Amy Adams and Jeremy Renner, debuted in third place on $24m (£19.1m).
The top five was rounded out by Almost Christmas with $15.6m (£12.4m) and Hacksaw Ridge on $10.8m (£8.6m).
Next week's box office figures will reveal how the highly anticipated Harry Potter prequel, Fantastic Beasts and Where To Find Them has performed on its opening weekend.
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Dr Strange has kept its place at the top of the US box office for a second week, cementing Disney's record-breaking year.