Joao Felix was ready League of Nations holders Portugal took the lead in the first half against Wales in Lisbon.
The former Chelsea striker fired in a shot from 20 yards that deflected off Danny Ward.
Wales came into the game on a four-match winless run under Craig Bellamy and are short on players.
Veteran superstar Cristiano Ronaldo went close with a couple of mid-range 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 beat Wales captain Ben Davies and into the net.
Wales have lost three of their four meetings with Portugal, with the exception of a 2-1 friendly win in May 1951 with goals from Mal Griffiths and Trevor Ford.