The Briton's 98th career victory, from his 100th pole position, was his third win in four races and sent him 14 points clear of Red Bull's Max Verstappen.
Verstappen finished second at the Algarve circuit with Mercedes' Valtteri Bottas completing the podium, and taking a bonus point for the fastest lap, after starting from pole position.
Verstappen, who passed the Briton with four laps to go only to have to hand back the lead for exceeding track limits, finished a mere 0.745 seconds behind after starting on pole position.
Mercedes won 13 of the 17 races last season, and have taken both titles for the last seven years, while once-dominant McLaren have not won a race since 2012.
F1 is still considering a Saturday sprint format, according to new head Stefano Domenicali.
The season will end with the Abu Dhabi Grand Prix at the Yas Marina track on December 13. It is unclear whether Hamilton will take part.
French driver Romain Grosjean had a miraculous escape from a fiery first-lap crash that ripped his car in two.
The 35-year-old Mercedes driver matched Ferrari great Michael Schumacher's seven titles in style, lapping sole rival and teammate Valtteri Bottas on a nightmare afternoon for the spinning Finn.
Hamilton took a record-extending 93rd career win at the Emilia Romagna Grand Prix as his Mercedes team clinched an unprecedented seventh successive Formula One constructors' title with four races to spare.
The Mercedes driver had equalled Ferrari great Michael Schumacher's record 91 wins at the previous race at the Nuerburgring.