The victory emerged Portugal second in Group A, with just a point behind Serbia who they host in their final game.
Ronaldo scored two penalties and rounded off the scoring with a stunning header as he recorded his emphatic 58th hat-trick for both club and country.
Bruno Fernandes and Joao Palhinha added the other goals for their national team.
Bruno Fernandes excellently flock a low shot into the bottom-right corner as the hosts went 3-0 up inside 18 minutes.
Nevertheless, all the news headlines will absolutely belong with his Manchester United team-mate who now has 115 international goals to his name.
Christiano Ronaldo has scored more international goals against Luxembourg (nine) than any other opponent.
The 36-year-old broke Iran striker Ali Daei's record of 109 goals last month.
Next month Fernando Santos's Portugal side travel to Ireland before then hosting Serbia in what could be a winner-takes-all fixture to qualify for the 2022 World Cup in Qatar.
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