Verstappen's incident led to a red flag with three laps remaining, which became a two-tour shootout following a second standing start, where Hamilton challenged Perez for the lead at the first corner.
The Mercedes driver's brakes were smoking heavily ahead of the second start, but he made the better getaway from the front row and was ahead of Perez as they braked for Turn 1.
But Hamilton's right-front wheel locked and he sailed into the deep run-off area, falling out of the points and eventually coming home 15th, as Perez ran clear in the lead to claim his first victory for Red Bull.
Over two hours earlier, Ferrari's Charles Leclerc had led briefly from pole before the long-time top three powered by, with the race split in two by a safety car period that followed Lance Stroll also suffering a dramatic tyre blowout along the main straight, before the Verstappen incident added an unexpected late coda.
At the initial start, the top three on the grid eased away, with Leclerc staying in command from pole as Hamilton and Verstappen slotted in behind in grid order, with Perez the main gainer as he moved from P6 to fourth by taking advantage of Carlos Sainz losing momentum fighting Pierre Gasly and then battling by the AlphaTauri into Turn 3 at the end of the back straight.
Leclerc ended the first lap just 0.3-seconds ahead, but his lead did not lost much longer as Hamilton was able to close in and shoot by as they ran back across the grid for the second time.
Debris falling ahead of the Turn 15 fast left where several cars have crashed this weekend appeared to cause Leclerc to cut the corner, which gave Hamilton the momentum he needed to get a run on the Ferrari and seal the lead.
Leclerc was able to stay with the Mercedes for several laps, with Verstappen in close attention behind, but when he dropped out of DRS range at the end of lap six of 51 the Red Bull bounced.
Just as lap seven began, Verstappen swept by on the outside run to Turn 1, with Perez doing likewise to drop Leclerc to fourth in similar fashion one tour later.
Hamilton was able to run clear of Verstappen's DRS for the next few laps, but the Red Bull was just beginning to close in when the pitstop phase kicked off.
Two laps after Leclerc came in at the end of lap nine from behind the three leaders, Hamilton came in to change his softs for hards, but a delay waiting for Pierre Gasly's AlphaTauri to pass by the Mercedes pits cost him significantly.
Verstappen was lighting up the timing screens on the next tour, his in-lap, but 1.9s stop for hards compared to Hamilton's 4.3s meant he came out comfortably ahead in the net lead.
Perez also delivered a stunning in-lap on the next time by, which became crucial as he was able to jump Hamilton too despite a slow left-rear change meaning he was stationary for 4.3s.
Hamilton had DRS to look to attack Perez into Turn 3 on his out-lap, but the Mercedes couldn't get close enough to make a move, as the net leaders settled down in their new order while running behind Sebastian Vettel's long-running Aston Martin.
Verstappen gradually eased away from his teammate as Hamilton chased Perez in the Mexican's DRS range for much of the next phase of the race – the trio cycling back into the proper lead when Vettel pitted for hards on lap 18, rejoining behind Leclerc, who lost out to Gasly in the stops, in sixth and seventh.
By lap 15, Verstappen's advantage over Perez was 3.1s, where it stabilised for the next 10 laps as the leaders made sure not to over consume their tyre life, with Hamilton eventually slipping out of Perez's DRS range during this stage.
A string of fastest laps as he lapped and then pulled away from Nikita Mazepin meant Verstappen's advantage reached five seconds just past the half-distance mark, with Perez losing time to both his teammate and Hamilton on the lap where he came to pass the Haas.
Verstappen's lead was approaching seven seconds when the race was interrupted by a shocking tyre failure for the yet-to-stop Stroll, who had started P19 but suffered a left-rear tyre blowout as he came to lap Mazepin as they ran down the main straight at the end of lap 30, with Stroll running in an elevated fourth place.
The tyre blowing out sent the Aston Martin spearing to the inside wall nose-first and coming to a stop near the high-speed pitlane entry, with debris strewn across the track and so the safety car was quickly deployed and the pitlane closed.
Stroll was able to climb out unharmed, with five laps passing behind the safety car as the wreckage was cleared.
The race restarted at the start of lap 36, with Verstappen dropping Perez as they reached the grid with the green flags waving and then racing clear to a two-second lead by the end of the first lap back at full speed.
Hamilton was got close to Perez at the restart but never looked like being able to make a move, as the top three again moved clear of the pack, which was soon headed by Vettel – who nipped by Leclerc exiting Turn 1 at the restart after the Ferrari had tried to repass Gasly, with the AlphaTauri then losing out in a drag race with the Aston down the main straight ahead of lap 37 beginning as Vettel gained two spots in less than one tour.
Verstappen quickly pulled out his lead again and looked in full control and easing to a second victory in succession, his advantage reaching 4.4s at the start of lap 46, at the end of which his race ended in shocking fashion.
Just before the Red Bull reached the grid hatching at top speed, his left rear tyre gave away in a similar fashion to Stroll – with the Red Bull pitched into the outside wall opposite the pits.
Verstappen was sent around several times after going into wall nose-first and as he climbed from his wrecked RB16B and kicked the destroyed left-rear tyre, the safety car had been called.
But after a few laps with the safety car leading the pack through the pits, the race was suspended – just after Red Bull had suggested to the FIA that such a development would allow all cars to change tyres given it had had no warning of Verstappen's failure, per team sporting director Jonathan Wheatley.
After a delay of 35 minutes, the final shootout took place with all the cars back on soft tyres, proceedings beginning again with another standing start restart, where it all went wrong for Hamilton and Perez's path to a second career win was eased, the Mexican winning by 1.3s.
Vettel came home second thanks to Hamilton's off, with Gasly fending off a determined attack by Leclerc on the final lap to seal third for AlphaTauri.
Lando Norris had battled back from a poor initial start to climb to eighth before the red flag, which was became seventh thanks to Verstappen's absence, and he gained two spots at the second start to rise to fifth, ending up very close to Leclerc as the Ferrari challenged Gasly.
Fernando Alonso had led a pack of four cars to take a second stop when the pitlane reopened just before the Stroll-incident safety car came in, but was set to finish at the tail end of the top 10 before the stoppage.
The Alpine driver also had an excellent second start to climb to sixth ahead of Yuki Tsunoda and Sainz, with Daniel Ricciardo and Kimi Raikkonen rounding out the top 10.
George Russell could not take the restart as he lost drive approaching the grid on the second warm-up lap and crawled back to the pits, where he joined Esteban Ocon as the other non-finisher.
Ocon stopped at the end of lap four after he reported a loss of power, with a puff of smoke coming from his car as he exited the final real corner before he pulled into the pits.
|1||Sergio Perez||Red Bull|
|2||Sebastian Vettel||Aston Martin||1.385|
|8||Carlos Sainz Jr.||Ferrari||7.709|
|10||Kimi Raikkonen||Alfa Romeo||9.576|
|11||Antonio Giovinazzi||Alfa Romeo||10.254|
|Max Verstappen||Red Bull|
|Lance Stroll||Aston Martin|