Diogo Dalot and Bruno Fernandes both started on Saturday evening, as Portugal hosted the Republic of Ireland in Lisbon.
The Reds pair were named in a strong line-up by Roberto Martinez, with the hosts aiming to make it three wins out of three in Group F, which also contains Hungary and Armenia.
Unsurprisingly, Portugal dominated much of the play, as Ireland were restricted to just two shots - neither of them being on target.
Heimir Hallgrimsson's side received plaudits for the way in which they defended resolutely, although Cristiano Ronaldo hit the post and fired wide twice after the break.
The former United man then had a golden opportunity to open the scoring from the spot, when Dara O'Shea was adjudged to have handled in the box 15 minutes from time.
However, Brentford keeper Caoimhin Kelleher denied the 40-year-old, to keep it goalless.
It looked set to be a frustrating night for Dalot and Fernandes, who were both substituted during the second half.
But, as the contest approached its denouement, Ruben Neves nodded home from Francisco Trincao's cross to send the hosts five points clear at the top of the group.
The former Wolves midfielder pointed to the sky in celebration, as a tribute to Diogo Jota in Portugal's first home game since the striker's death in July.