After drawing level with Michael Schumacher's mark of 91 victories at the Eifel Grand Prix last time out, Hamilton sealed a landmark triumph in Portimao to cement his status as one of the all-time greats.
The Mercedes driver extended his championship lead over team-mate Valtteri Bottas to 77 points to improve his chances of matching Schumacher's record haul of seven titles this year.
Pole-sitter Hamilton fell back to third on the second lap but was not to be denied his moment of unprecedented glory, with Bottas having to settle for second ahead of Max Verstappen.
Light rain fell at the start of an action-packed opening lap, with Bottas regaining second from Verstappen – who then collided with Sergio Perez and slipped to fifth – before passing Hamilton through Turn Eight to take the lead.
Carlos Sainz also overtook Hamilton on the opening lap and went past Bottas on the next, but by lap eight the Spaniard's soft tyres started to fade and he slipped back behind the Mercedes duo and Verstappen.
The reigning champion started complaining about the state of his tyres but was soon on the back of Bottas and returned to first place with the help of DRS into Turn One at the start of lap 20.
Hamilton was then able to establish an eight-second cushion at the front and he and Bottas switched onto the hard compound for the final third of the race.
Having successfully navigated the early drama, Hamilton was able to cruise to the chequered flag – despite telling his team he was suffering with cramp – and add to an incredible haul of victories that will take some serious beating.
Hamilton this weekend improved the F1 record he holds for the most wins and pole positions at different grands prix to 27 – he has taken part in 31.
It was also the 32nd circuit he has competed at in the series and he now has 28 wins and 29 pole positions across those. Magny-Cours, New Delhi and Istanbul are the only places at which he has failed to start from the front of the grid, but Turkey is coming up on the calendar.