Ronaldo got the ball rolling early on with a tap-in, before further goals from Joao Felix and Bernardo Silva made it 3-0 inside 18 minutes, while Ronaldo added another just after the half-hour mark.
Second-half goals from substitutes Otavio and Rafael Leao completed another routine victory for Portugal after their 4-0 win over Liechtenstein to kick off their qualifying campaign and the rein of new head coach Roberto Martinez.
They sit top of Group J after two games, two points ahead of Slovakia in second after their win against Bosnia-Herzegovina.
Portugal took the lead in the ninth minute when a ball to the far post from Bruno Fernandes was headed back across goal by Nuno Mendes, giving Ronaldo a simple tap-in from close range.
The advantage was doubled just six minutes later, as this time Silva's inswinging ball from the right was nodded across Luxembourg goalkeeper Anthony Moris and into the corner of the net by Joao Felix.
Silva got on the end of a long pass from Joao Palhinha to head in the third, while Ronaldo grabbed his second and Portugal's fourth in the 31st minute when Fernandes played him through on goal, with the Al Nassr striker placing his left-foot shot low to Moris' right.
Portugal had another in the 77th minute when Leao and Otavio combined, with the latter heading home the Milan attacker's cross from the left.
Leao saw a late penalty saved by Moris after winning it himself, but made up for it shortly after when his run inside from the left ended with a composed finish.
Roberto Martinez's team did not let up after Rafael Leao lashed them ahead in the 24th minute, with Matheus Nunes and Bruno Fernandes putting them three to the good by half-time.
Bruma made matters worse for Sweden before in-form Sporting CP forward Viktor Gyokeres netted at the other end, albeit that goal should have been disallowed for offside.
Goncalo Ramos rounded off Portugal's rout just after the hour, though Gustaf Nilsson did grab another consolation for Sweden in the final stages.
Leao's strike was just his fourth for the Selecao, with the winger hitting his shot sweetly after controlling the rebound from Bernardo Silva's effort off the woodwork.
Portugal's control was cemented just after the half-hour mark, as Silva set up his Manchester City team-mate Nunes for a composed finish from outside the box.
Sweden were punished for more slack defending on the stroke of half-time – Fernandes left free in the six-yard box to power a shot high into the back of the net, taking his international tally to 20 goals.
The hosts started the second half with the same intensity, and Fernandes' pressure paid off when he blocked a clearance and set Bruma up for a tap-in. Just 91 seconds later, Gyokeres pulled one back for Sweden from an offside position, but with no VAR, the goal stood.
Ramos restored Portugal's four-goal lead shortly after, with his eighth goal in 10 international appearances adding further gloss to another fine win under Martinez, though Nilsson – who had earlier tested Rui Patricio with an audacious attempt – ensured Sweden had the final word.
No Ronaldo, no problem
Portugal were without their biggest star in Guimaraes, with Cristiano Ronaldo the most notable absence from the team sheet. But it is not like they struggled without the 39-year-old.
The Selecao have scored 36 goals in their perfect Euro 2024 qualifying campaign, the most of any nation during that time, and they clocked up another five with ease.
Perhaps even more pleasing to their coach, the goals were spread among his midfield and forward line, with Bruma also coming off the bench to make an impact.
They might have gone under the radar, but Portugal could be the ones to watch in Germany come June.
Tomasson's big changes fail to pay off
After playing in a rigid 4-4-2 formation under Janne Andersson, Sweden deployed a more attacking set-up under Jon Dahl Tomasson on Thursday, with Newcastle United star Alexander Isak playing behind Gyokeres, who is thriving in Portugal this season.
It showed the promise of paying off in the second half, with Gyokeres getting his goal just before the hour-mark, but by then it was already too late for them to mount a real comeback, and Nilsson's effort did nothing more than restore a tad more pride.
Three of Portugal's goals were simple tap-ins, with the Selecao's scorers left with an empty net to aim for, and that slack defending will frustrate Tomasson.
Ronaldo saw an extra-time spot-kick saved by Jan Oblak as Portugal played out a goalless draw in Monday's tie, only to scrape through to the quarter-finals on penalties.
The five-time Ballon d'Or winner scored in the shoot-out but is yet to net in regular play at this tournament, despite amassing a competition-high 20 shots worth 2.75 expected goals (xG).
He has failed to score in his last eight appearances at the World Cup or European Championships, having netted 10 times in his previous nine between 2018 and 2022.
When asked about Ronaldo's tears at Thursday's pre-match press conference, Silva said: "We're humans and he felt emotional when he missed a penalty.
"It's acceptable, isn't it? Sometimes you react in ways you don't expect... he felt he could have done better in that moment.
"He cries for a bit, which is how humans deal with emotions sometimes.
"So I don't see any reason for people to discuss it. Obviously people will, because that's the business."
Though Portugal impressed as they beat Turkiye 3-0 in their second group-stage match, they have disappointed in their other games and been criticised at home over a lack of attacking thrust.
Asked about that criticism, Silva said: "We understand it, it's part of the business, it's the reason why we earn so much money and we are able to give our families and friends a better life.
"We don't complain about the criticism, it's for good and for bad, it's our job.
"When it comes to June and a World Cup or Euros, everyone thinks they're a manager. We get that and we accept that."
Mac Allister, 24, is enjoying a career-best season, with his five goals in 17 Premier League fixtures already matching his best ever tally for a full league season.
The talented creative midfielder also made six starts for Argentina during their march to victory at the Qatar World Cup, scoring his first senior international goal during a 2-0 win over Poland in the group stage.
His emergence as a player capable of shining on the world stage, as well as his contribution to Brighton's terrific season, has apparently caught the eye of City boss Pep Guardiola.
TOP STORY – CITY VIEW MAC ALLISTER AS IDEAL GUNDOGAN REPLACEMENT
According to Fichajes, Gundogan is expected to leave City when his contract expires at the end of the season, and Bernardo Silva could follow if he gets his wish with a LaLiga move.
The report states Guardiola is a big fan of Mac Allister, and believes he has proven himself as a capable Premier League producer.
Fichajes claim Brighton have set an asking price in the range of £40million, indicating they are more willing to part ways with him than 21-year-old Moises Caicedo, with both of their contracts expiring in 2025.
ROUND-UP
– ESPN is reporting Napoli will hold firm with an asking price of at least €100m (£90m) for 24-year-old striker Victor Osimhen, who has strong interest from Manchester United and Paris Saint-Germain.
– According to 90min, Chelsea's top priority now is sorting out a contract extension for 24-year-old England international Mason Mount.
– Mason Greenwoodwill look to revive his career in Chinaif United decide to let him go, per the Sun.
– Caught Offside is reporting West Ham and Evertonwill have to return after the season if they want to sign 27-year-old winger Sheraldo Becker, with Union Berlin unwilling to deal in January due to their strong league position.
The United club captain is contracted until 2025 and his deal includes £200,000 per week wages.
Maguire has only started one of United's last eight Premier League games and did not play in Thursday's Europa League win over Real Betis.
TOP STORY – PSG SET FOR SHOCK MAGUIRE MOVE
Paris Saint-Germain are set for a shock £50million (€56m) move for Manchester United defender Harry Maguire, according to The Sun.
It has been claimed that Maguire is among a list of players that United are willing to sell in the off-season with Newcastle United and West Hamreportedly interested.
According to The Sun's report, PSG tabled a deal for Maguire in January, but time ran out to finalise it and the French champions will move again for him.
ROUND-UP
– The Independent reports Real Madrid are plotting an overhaul to bring in a new generation of young stars, with Manchester City's Erling Haaland top of the list along with Borussia Dortmund's Jude Bellingham.
– The Guardian reports Manchester United will enter the race to sign Chelsea midfielder Mason Mount, with interest also from Liverpool and Newcastle United. Mount and Chelsea are currently in the middle of a contract dispute, potentially making him available, with United viewing him as a cheaper alternative to Bellingham.
– Barcelona are in the market to sign Manchester City's Portuguese full-back Joao Canceloif Bayern Munich do not make permanent his loan spell, claims Sport.
– Newcastle are circling to sign Southampton free-kick specialist James Ward-Prowse, according to Football Insider. Newcastle are one of numerous Premier League clubs interested in him.
– Gazzetta dello Sport reports Inter have tabled a two-year contract offer to Edin Dzeko amid interest from West Ham.
– L'Equipe claims PSG are ramping up their bid to sign Manchester City midfielder Bernardo Silva in the off-season.
Manchester United have been linked with the ex-Tottenham manager, who took over at PSG in January last year.
The Red Devils dismissed Ole Gunnar Solskjaer in November, with Ralf Rangnick taking over on an interim basis.
TOP STORY – LOS BLANCOS KEEN ON POCHETTINO
Real Madrid are set to rival Manchester United to land Pochettino this off-season, claims the Daily Mail.
The Red Devils are understood to be circling for the Argentine, who is reportedly unhappy at Paris Saint-Germain.
But the report claims Madrid have doubts over current boss Carlo Ancelotti's future and believe that Pochettino is obtainable in the off-season.
ROUND-UP
- Manchester City's Portugal midfielder Bernardo Silva is dreaming of a switch to join Real Madrid, claims Calciomercato.
- Calciomercato also reports that Inter are monitoring Gabriel Jesus' status at City, with a view to bolstering their attack.
- Nicolo Schira reports that Atalanta are keen to move for Torino's Italy international striker Andrea Belotti in the off-season when he is a free agent.
- TuttoMercatoWeb claims Arsenal, Newcastle United, Borussia Dortmund and Inter are all in the race to sign Lille's Canadian forward Jonathan David.
- GiveMeSport claims Liverpool are "seriously interested" in West Ham United's Jarrod Bowen.
- Roma are keen on signing Barcelona's USA international defender Sergino Dest according to Fichajes.
