Bruno and fellow Red Diogo Dalot both started at Estadio Algarve, with Fernandes looking to follow up his match-winning goal in the 1-0 triumph over Slovakia on Friday with another prolific performance, but he turned provider as Portugal took an early lead.
Following a clearance from a corner, United's no.8 curled a delightful cross with the outside of his boot straight onto the head of Goncalo Inacio and the centre-back rose high and directed the ball beyond Anthony Moris to give the hosts the advantage.
It wasn't long before the 2016 European champions were two goals to the good either, as Bruno's typically terrier-like hassling of the Luxembourg defence resulted in the midfielder winning possession before feeding Bernardo Silva.