The Dutchman, who took his second successive drivers' title in Japan this month, lapped the Circuit of the Americas with a best time of one minute 35.825 seconds on the soft tyres.
Ferrari's Charles Leclerc (25), who will have a 10-place grid penalty for Sunday's race due to power unit changes exceeding his season's allocation, was 0.320 slower in dry but windy conditions with team mate Carlos Sainz (28) third.
The Ferrari drivers had led both practice sessions on Friday.
Red Bull's Sergio Perez (32), who has a five-place grid penalty, was fourth fastest and seven times world champion Lewis Hamilton (37) was fifth for Mercedes.
Ferrari need to score 19 points more than Red Bull to keep the championship leaders waiting for another week for their first constructors' title since 2013.
Verstappen has won 12 of 18 races so far this season and a 13th would equal the single-season record held by German greats Michael Schumacher and Sebastian Vettel (35).
