The Red Bull pair took advantage of Mercedes' reluctance to show their full potential in the closing minutes of the session.
Dutch teenager Max Verstappen topped the times ahead of his Red Bull team-mate Australian Daniel Ricciardo in Saturday morning's disjointed third and final practice ahead of Sunday's United States Grand Prix.
The Red Bull pair took advantage of Mercedes' reluctance to show their full potential in the closing minutes of the session as Kimi Raikkonen clocked the third best time for Ferrari.
Defending three-time champion Lewis Hamilton was fourth fastest and his Mercedes team-mate and championship leader Nico Rosberg sixth, but both ran late without clocking laps on super-soft tyres.
Verstappen's best lap in one minute and 36.766 seconds was 0.266 seconds quicker than Ricciardo, both men running on super-softs. Raikkonen was half a second adrift in third.
Hamilton was a further two-tenths slower in fourth place and three-tenths ahead of Rosberg, but on a bright clear day at the Circuit of the Americas there were few clues of true performance given away by the leading teams when they ran their qualifying simulation laps in the final minutes.
Four-time champion Sebastian Vettel was sixth for Ferrari ahead of Renault-bound German compatriot Nico Hulkeberg of Force India, Valtteri Bottas of Williams and the two McLaren-Hondas of Jenson Button and Fernando Alonso.
Hamilton, using a car fitted with a new fuel injection system overnight and revised brake settings, showed his disappointment at being released too late to clock a faster lap.
"That was really poor timing guys," he said on the team radio. Rosberg, also late out, aborted his best lap.
The session was interrupted by a red flag when Pascal Wehrlein spun off in his Manor car after half an hour and also featured two punctures for Carlos Sainz in his Toro Rosso.
Hamilton's repaired car was not ready until mid-way through the session - the mechanics having worked for the entire night bar three hours - and was soon thrown into action.
"We are now running the engine that was first used on Lewis?s car at Spa, at the Belgian Grand Prix," said Mercedes technical director Paddy Lowe.
After running it on Friday, we found that there was a small fault in the fuel system. It's not a serious problem, but for precautionary reasons we felt we should put a better one in there.
The people working on the engine were here until 1 am and then another group of people were in at 4 am to do some more work and then the main group were back at six."
Hamilton used his spare time, while waiting for his car, as an opportunity to show Hollywood actor Christoph Waltz around the Mercedes team garage.
He looked much happier than he was on Friday when he conceded that he had brake problems.
"We made some brake-setting changes which were disastrous, said Hamilton. I was struggling to finish a lap without over-steer, but we?ll fix that and I am sure we?ll get back on the pace."
Russian Daniil Kvyat, confirmed as remaining with Toro Rosso for another year by team on Saturday morning, wound up 14th fastest, one place ahead of Sainz.