Max Verstappen secured the record for the most victories in a season as Red Bull outsmarted Mercedes at a strategy-driven Mexico City Grand Prix.
The double world champion secured his 14th win of the campaign, surpassing the 13 collected by Michael Schumacher and Sebastian Vettel before him.
The fight between Red Bull and Mercedes hinged on tyre choice, with the world championship-winning team opting for a soft-medium one-stop compared to the medium-hard strategy deployed by the Silver Arrows.
The switch to the hardest compound ultimately cost Hamilton the opportunity to fight his rival from last season, Verstappen eventually winning by some 15 seconds.
Sergio Perez delighted his home crowd by taking his second podium at the Autodromo Hermanos Rodriguez in a row, with George Russell trailing in fourth.
All eyes were focused on the run down to turn one with Russell alongside polesitter Verstappen.
The Briton offered no challenge when tentative on the brakes into the first apex, instead finding himself under attack from his team-mate.
Mercedes drivers unhappy with strategy
The Mercedes skirmish allowed Perez a chance to make his way into third at turn four, the Red Bull driver duly obliging.
Verstappen was 1.3secs ahead of Hamilton at the end of the first lap, a gap that only extended as far as two seconds by the end of the Dutchman's first stint.
The race settled into a rhythm as teams began a game of Pirelli-tyre chess, strategic messages being played out on the radio.
Graining for both Red Bulls saw Perez pull the trigger with a switch to mediums on lap 23, a move duplicated by his team-mate two laps later.
But with both charging on fresher rubber, Mercedes decided to only extend Hamilton by a further four laps despite starting on the durable medium tyres.
Russell only reached lap 34, with both Mercedes drivers disgruntled to have been moved to the hard tyres.
The gap was ever-growing between the top two drivers, though Hamilton's race engineer Peter Bonnington was adamant the medium tyres on his rival would fall away at the end.
That never transpired, however, and despite a small flicker of drama as Fernando Alonso pulled to the side of the track on lap 65 to trigger a virtual safety car, there was nothing Mercedes could do to recover.
Russell pitted on lap 70 to attempt the fastest lap, fitting a set of soft tyres and achieving the feat.
Ferrari nowhere as Alonso fumes
Ferrari had an anonymous race, and would have finished over half a minute adrift of fourth-placed Russell without the late stop for the Mercedes.
Carlos Sainz finished ahead of team-mate Charles Leclerc.
They finished ahead of a resurgent Daniel Ricciardo, who made the alternate medium-soft strategy work to perfection to finish seventh, despite a 10-second penalty for knocking Yuki Tsunoda out of the race when colliding at turn six, with the effort further underlining the confusion regarding Mercedes' strategy.
Esteban Ocon was eighth in the sole remaining Alpine, his team-mate furious having retired from seventh on the road with yet another engine issue.
Lando Norris fought to ninth ahead of Valtteri Bottas, who was unable to convert his strong qualifying performance into a top-eight.
Pierre Gasly was again hampered by a five-second penalty, this time for forcing Lance Stroll wide at turn four early in the race, and finished just outside the points, ahead of Alex Albon and Zhou Guanyu.
Sebastian Vettel was 14th ahead of team-mate Lance Stroll, Mick Schumacher was 16th for Haas ahead of Kevin Magnussen and Nicholas Latifi, who was the last of the finishers.