Mannix, 52, replaces Sebastien Bertrank, who lasted just a month in the role having succeeded Patrice Lagisquet.
The veteran Frenchman guided Os Lobos (The Wolves) to a victory over Fiji and a draw with Georgia at last year's Rugby World Cup.
Ex-playmaker Mannix has had coaching spells with French clubs including Pau, Racing 92 and more recently second-tier Biarritz. He played for outfits such as the Hurricanes, Sale and Gloucester and will aim to qualify Portugal for the 2027 World Cup in Australia.
A large number of the Portugal set-up play their club rugby in France including in-form wingers Raffaele Costa Stori and Rodrigo Marta.
"Simon is a very experienced coach," FPR president Carlos Amado da Silva said.
"I am convinced that the style of play he implemented in his previous teams is the most suitable for our national team.
"Furthermore, he has a strong connection with France, both with the players and the clubs, which makes him the ideal profile we needed."
Mannix's first games in charge are both away, on July 13 with Namibia and a maiden Test against four-time World Cup winners South Africa a week later.
