The 1-6, 6-3, 6-4 victory against the Spaniard, which was sealed on a fifth match point, will cast 16th-ranked Wawrinka as the villain when he takes on home favourite Portuguese wild card Gastao Elias.
Elias won only the second ATP-level match of his career when he beat Denis Istomin 3-6, 6-1, 6-4.
Wawrinka, a semi-finalist in his Portugal debut last year, admitted that he might have arrived too early at the event where he had a bye into the second round and the latest possible start.
The Swiss even tweeted this week that he bought a PlayStation to help pass some of his free time after coming in last Friday night from Geneva.
"Maybe I arrived a bit early, but the first match of the tournament is always tough, especially if the guy already has played a match," he said of Ramos, whom he has now beaten four times, including a February meeting in Argentina.
The Swiss made a fast recovery after number 57 Ramos ran off with the first set.
But closing down the contest was tough, with Wawrinka failing on four match points in the penultimate game on his opponent's serve.
He finally got the win a game later after coming from 0-40 down.
"It's true I had my chances and maybe I was thinking about those that I missed," said the 28-year-old, who is now coached by Swede Magnus Norman.