Juventus forward Ronaldo scored both goals in last month's 2-0 victory in the reverse fixture but was ruled out of this match after testing positive for coronavirus on Tuesday.
Jota, brought back into the line-up for Wednesday's clash in Lisbon, stepped up by playing in Bernardo Silva for the opener and then scoring the second before half-time.
William Carvalho headed against the post inside four minutes when left unmarked at the back post but the hosts did not have to wait much longer to find a breakthrough.
Bruno Fernandes turned over possession, slipped in Jota and the Liverpool winger squared for Silva to curl past Robin Olsen with a first-time finish from 10 yards.
Portugal survived a scare when Marcus Berg's shot hit the post and they had some breathing space when Jota controlled Joao Cancelo's pass and tucked a shot in a minute before the break.
Rui Patricio produced a couple of good saves to keep out Berg and Viktor Claesson early in the second half as Sweden - without a point from four Group A3 games - pushed for a route back into the game.
But it was Fernando Santos' men who scored the game's third goal through Jota, who took the ball past a few players and picked his spot past Olsen after being found by Carvalho.
What does it mean? Ronaldo-less Portugal win again
Portugal put four goals past Croatia in Ronaldo's absence in their opening Nations League game and looked very good in an attacking sense here.
Santos' men had 16 shots in total - six of those on target - with Premier League stars Jota, Fernandes and Silva linking up superbly at times.
The European champions stay above France, who were 2-1 winners against Croatia in Zagreb, on goal difference, while Sweden are still seeking their first point.
Cancelo shines out wide
Jota will steal the headlines thanks to his two goals and assist but right-back Cancelo was an unsung hero for Portugal at both ends of the field.
His pass for Jota's opening goal was sublime - one of two chances he created in a game that also saw the defender top his team's charts for open play crosses (four).
Joao Felix fails to fire
The last four games Joao Felix had been involved in prior today finished in 0-0 draws - two for Atletico Madrid and two for Portugal.
He was again on the periphery during his 75 minutes on the pitch here, firing over from a good chance in the second half and managing just 23 touches of the ball - the fewest of any home starter.
Portugal host Andorra in a friendly in their next match on November 11, while a trip to Denmark awaits Sweden - also a friendly - on their return to action next month.