Mercedes made a two-stop plan work to perfection around Barcelona's Circuit de Catalunya to elevate Hamilton into a 14-point cushion over Max Verstappen who again had to settle for the runner-up spot for the third time this year.
It was reminiscent of Hamilton's 2019 win in Hungary when he again hunted down Verstappen over the closing third of the race after making a second stop late on and used fresher tyres compared to ageing rubber for the Dutch driver to claim the win.
On this occasion, with 24 laps remaining of the 66, Hamilton emerged on fresh tyres and closed down a gap of just over 23 seconds to take the lead and victory on lap 60.
Verstappen pitted immediately after to take on a new set of soft tyres and at least claim the point for fastest lap, with Valtteri Bottas third for the third time in four races.
It had all started so well for Red Bull as from their first front-row start since 2011, Verstappen's reactions once the five red lights disappeared appeared to be marginally quicker than that of Hamilton.
It allowed the Dutch driver to sit in the slipstream for a moment before pulling out to take the inside line into turn one, doing enough to force Hamilton wide.
How the title rivals did not touch was remarkable as the respect between them they have previously mentioned again came to the fore.
Verstappen then went on to open a gap of 1.5 seconds to Hamilton after the first lap, which Hamilton managed to control up until a safety car was deployed at the start of lap nine
That was for AlphaTauri's Yuki Tsunoda stopping on track with a suspected power unit failure on the outside of turn 10.
By that stage, Verstappen and Hamilton had stretched their advantage to third-place Charles Leclerc in his Ferrari to almost 10 seconds.
Leclerc had produced a fine move on Bottas around the outside of turn three on lap one to claim third from the Finn who was attacking the Monégasque when the safety car was summoned for the fourth successive race this season.
After just two laps on track for safety car driver Bernd Maylander, following the quick removal of Tsunoda's car, Verstappen then comfortably led away the restart.
What followed was typically processional for this circuit until the round of pit stops, and the point where Red Bull's lightning precision went awry.
At that point, at the end of lap 23, Hamilton had closed to within half-a-second of Verstappen and appeared prime for the undercut, in particular, when Red Bull's pit crew delivered a rare blunder.
As Verstappen was pulling into his pit box, the left-rear tyre was only just coming out of the garage, leading to a 4.2s stop for a team that normally turns around its cars in two seconds.
Mercedes, though, opted not to pit Hamilton immediately, instead opting for greater tyre life as they eventually brought in Hamilton five laps later.
It appeared a strange decision, notably as Mercedes had managed to perform a cut on Leclerc to reclaim third for Bottas.
Within five laps Hamilton's fresher tyres had allowed him to close to within a second to Verstappen albeit never getting within range to attempt an overtake.
Mercedes then pulled a surprise by pitting Hamilton for a second time after 42 laps, taking on a set of scrubbed medium tyres and leaving him with a gap of 23.289s to claw back in 24 laps as Red Bull opted to keep Verstappen out.
Hamilton had dropped into third, so when he came up behind Bottas on lap 52, there was an instruction from the pit wall for him not to hold up the Briton.
Bottas, however, proceeded to do so for two-thirds of a lap, forcing Hamilton to make a move through turn 10 and costing him three-tenths of a second in his charge.
But it failed to deny Hamilton the win, with Leclerc fourth behind Verstappen and Bottas, followed by the second Red Bull of Sergio Perez.
Perez, who made up three places from ninth by the start of lap two, later pulled off a fine move on McLaren's Daniel Ricciardo around the outside of turn one on lap 45 to claim fifth spot.
Ricciardo had to settle for sixth, with the Australian ahead of Ferrari's Carlos Sainz, the second McLaren of Lando Norris, Alpine's Esteban Ocon and Pierre Gasly for AlphaTauri, despite the Frenchman taking a five-second penalty early on for being out of position in his pit box at the start.
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