- Bruno Fernandes (32', 65')
The Manchester United midfielder scored a goal in each half as Portugal booked their place to Qatar later this year.
The result sees Portugal qualify for the World Cup for a sixth consecutive time. It is likely to be Cristiano Ronaldo's last for his country although he dismissed reports of retirement before the playoff.
"Goal accomplished,'' Ronaldo said on Instagram after the match. "We made it to the World Cup in Qatar. We are where we deserve to be.''
Macedonia were unable to replicate their shock win over European champions Italy but gave a good account of themselves throughout the 90 minutes.
"This win will remain in a special place for me because we have achieved our aim," Fernandes said in his postmatch interview. "That was the most important thing. I think Portugal played better.
"We've had better performances, but this is one of the highlights because it guarantees access to the World Cup.
"The important thing is to help the team. I'm not here to score, I'm here to help. If I can help with goals, I'm happy to do so. Any player likes to score. But the main aim is to help however I can. That's what I did and what I have done in the past."
Portugal took the lead after 22 minutes when Fernandes intercepted a poor pass in midfield and exchanged passes with Ronaldo before producing a fine finish into the corner.
Portugal controlled the match from that moment and doubled their lead in the second half after 65 minutes when Fernandes got on the end of a fine counter attack to convert from close range.
Roared on by 50,000 fans at a sold-out Dragao Stadium in Porto, Portugal dominated the game from the start but struggled to break down the strong North Macedonian defence, managing only three shots on target despite having almost 70% possession.
Fernando Santos' team then ran down the clock, celebrating at the final whistle with their joyful fans who remained in the stands for more than 15 minutes after the game, singing as the players completed a victory lap holding a huge Portugal flag.
Portugal, who won the 2016 European Championship in France, qualified for a sixth straight World Cup finals and have not missed a major international competition in the last 20 years.
They were pushed into the playoffs after finishing second in Group A, having lost their final game at home to Serbia 2-1 last November.
That had left them needing to win two consecutive elimination games to qualify, with last week's win over Turkey, where they survived late drama, setting up a decider against Macedonia.
It was a nervous occasion in Porto on Tuesday but Portugal dominated and avoided any surprises from the underdogs, who did not have a shot on target.
"My players showed a fantastic attitude," Santos said. "There was a sense of collectiveness, we dominated, we created chances and we scored. The fans were fantastic. It's a deserved win.
"We fully merit to be in the World Cup. My conscience is clear. I have already won two competitions [Euro 2016 and UEFA Nations League 2019] and I dream a lot of winning a third."
- Anthony Taylor