Joao Felix was on target as Nations League holders Portugal took a first-half lead against Wales in Lisbon.
The former Chelsea forward fired in a shot from 20 yards which took a deflection and beat Danny Ward.
Wales came into the game on a four-match winless streak under Craig Bellamy and are without a raft of players.
Veteran superstar Cristiano Ronaldo went close with a couple of half chances before his Al-Nassr team-mate Felix broke the deadlock.
Left-back Nuno Mendes did well to find space behind Ethan Ampadu and pulled the ball back for Felix, whose shot hit Wales captain Ben Davies and span into the net.
Wales have lost three of their four meetings with Portugal, with the exception a 2-1 friendly win in May 1951 with goals from Mal Griffiths and Trevor Ford.