The Euro 2016 hosts have not failed to beat Portugal since 1975 and the signs looked ominous from the off for the visitors to the Stade de France.
Karim Benzema opened the scoring in the third minute when he reacted quickest after Portugal failed to clear their lines from an Antoine Griezmann cross.
Portugal – under the stewardship of Fernando Santos for the first time – fought their way back into the match after a shaky start, but struggled to find their way through a resolute home defence.
Cristiano Ronaldo came closest to an equaliser early in the second half, but Steve Mandanda - making his first France outing since suffering a serious neck injury that ruled him out of the World Cup - got down brilliantly to his right to keep out the header.
Paul Pogba's tidy finish then doubled France's advantage in the 69th minute, before Ricardo Quaresma scored his side's only goal from the penalty spot.
Santos, who will begin an eight-match touchline ban in Tuesday's Euro 2016 qualifier with Denmark, made six changes to the side that lost 1-0 to Albania in Portugal's opening Group I game, with captain Ronaldo back in the XI after missing that match through injury.
However, the Real Madrid forward's return failed to have an instant impact on his side's fortunes, as another Santiago Bernabeu marksman broke the deadlock.
Griezmann's cross from the left rolled all the way through for Bacary Sagna, whose powerful shot was parried to an unmarked Benzema – the 26-year-old calmly touching the ball home from close range.
Griezmann tormented the Portugal defence in the early stages and it took an assured stop from Rui Patricio to keep out the Atletico Madrid man's effort with the outside of his boot five minutes later.
Portugal started to find their rhythm as the half progressed, but Nani pulled a left-footed effort wide of the post, before Andre Gomes blasted a shot high and wide after a clever turn on the edge of the box.
Having watched Tiago come out of international retirement to take his place in the starting XI, Ricardo Carvalho came off the bench at half-time to make his first Portugal appearance in more than three years.
And Portugal almost pulled level six minutes after the break when a Ronaldo header drew a superb diving save from Mandanda – in for Hugo Lloris, who was only fit enough for the bench after picking up a minor injury.
France seemingly put the game to bed in the 69th minute, when Pogba side-footed into the bottom right-hand corner from a Benzema pass, following good work from Patrice Evra along the byline.
Blaise Matuidi should have made it 3-0 less then a minute later, but his left-footed shot curled agonisingly wide of the target.
Ronaldo saw a 74th-minute strike deflect wide off clubmate Raphael Varane, and accused the defender of handball before being withdrawn for Joao Mario.
The skipper's replacement was then caught by Pogba in the box and, with Ronaldo no longer available to step up to the mark, Quaresma duly converted, though it proved to be merely a consolation for Portugal.
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