Ronaldo had missed Portugal's past two friendlies due to a knee injury but made a comeback and played 65 minutes as his country wrapped up preparations for the FIFA World Cup with a comprehensive win in New Jersey.
A first-half brace from Hugo Almeida and a Richard Keogh own goal set Portugal on their way and provided a boost ahead of Sunday's Group G opener against Germany in Brazil.
Almeida opened the scoring in just the second minute with a powerful close-range header - his first international goal since March last year - and Ireland defender Keogh helped Portugal into a 2-0 lead with 25 minutes remaining in the half.
The contest was over before the break thanks to Almeida's 37th-minute goal as Portugal extended their unbeaten streak to eight games, having not tasted defeat since September's 3-1 loss to Brazil in an international friendly in the United States.
James McClean pulled a goal back for Ireland six minutes into the second half to salvage some pride following a poor performance, though Vieirinha and Fabio Coentrao struck inside the final 13 minutes as Portugal ended their three-game winless streak against the Irish.
Paulo Bento made seven changes to the team that beat Mexico in Massachusetts on Friday, with Ronaldo a noticeable inclusion in the starting XI, along with Raul Meireles, who had been suffering from a thigh injury.
Goalkeeper Patricio, Ricardo Costa, Ruben Amorim, William Carvalho and Varela all came into the line-up, while Eduardo, Bruno Alves, Joao Pereira, Nani, Miguel Veloso, Vieirinha and Eder dropped out.
Portugal's Irish counterparts also made a number of changes, with only David Forde, Keogh and Stephen Kelly retaining their spots following Friday's draw against Costa Rica.
Boosted by Ronaldo's return, Bento's men made a high-tempo start to proceedings and Ireland struggled to cope as Portugal took the lead just two minutes into the match courtesy of Almeida's powerful header.
Ireland lost possession in attack and Portugal pounced, with Silvestre Varela delivering an inch-perfect cross from the right-hand side for Almeida, who ended his goal drought for Portugal which stood at eight games.
Portugal almost doubled their lead in the 13th minute after Ireland surrendered possession again, this time in their own half, but goalkeeper Forde was on hand to deny Ronaldo and Meireles on the rebound.
Ronaldo continued to torment Ireland and after hitting the post from a free-kick, he linked up with Real team-mate Coentrao as Portugal went two goals ahead in the 20th minute, albeit fortuitously.
The Portugal skipper played a back-heel to Coentrao, whose cross from outside the box took a wicked deflection off Keogh and wrong-footed Forde as the ball looped into the net.
It got worse for Ireland eight minutes before the half-time break, when Forde failed to deal with Ronaldo's header and Almeida reacted quickest to scramble the ball over the line for his second goal.
The interval provided some welcome relief for Ireland, who emerged from the tunnel set on reducing the deficit early and they did so in the 52nd minute through Wigan Athletic midfielder McClean after Portugal switched off in defence.
Ireland were clearly the dominant team during the second half but despite taking the foot off the accelerator, Portugal still managed to restore their three-goal lead and add some icing on the cake inside the final 13 minutes.
Portugal broke quickly and although Forde saved the initial effort, he was powerless to prevent Vieirinha from firing home the rebound.
And Portugal completed the rout five minutes later after Nani played through Coentrao with the outside of his foot, before the Real defender placed the ball beyond Forde.
