The former Swansea City striker was the main threat in the opening stages of the match, and sent another effort narrowly wide shortly afterwards before William Carvalho looped a header over the top.
The chances continued to arrive for the hosts, with Nani and Joao Mario both coming close before the European champions finally broke the deadlock shortly before the half-hour mark.
That proved to be the only time his goal was breached in the opening 45 minutes, though, despite another string of chances for Eder before the first half came to an end.
It was in the second half that Portugal turned their dominance into goals, although it looked like being another frustrating 45 minutes when Nani, Bernardo Silva and Mario missed chances in the opening 10 minutes.
The hosts did finally double their advantage to give themselves a well-deserved cushion, with stand-in skipper Nani glancing a finish into the far corner from Andre Silva's cross.
Silva was once again the provider just three minutes later to create a glorious chance for Mario, but the new Inter Milan midfielder somehow failed to extend the hosts' lead further.
Mario then clipped the crossbar with an attempted cross before Gibraltar finally created their first chance of the match with less than 20 minutes remaining, only for Mickey Yome to slice wide when one on one with the keeper.
That chance seemed to spark Portugal into life, and they soon took complete control of the contest with a spell of three goals in six minutes. Joao Cancelo started the blitz off on his debut, smashing a thunderbolt in off the crossbar having been teed up by Silva.
Silva opened his international account himself moments later, although he had Jamie Robba to thank as the replacement Gibraltar keeper allowed the Monaco midfielder's tame shot to creep under his body and in.
Pepe then capped off the scoring with Portugal's fifth of the evening, cushioning a header back across goal and in to seal a comfortable victory as the hosts began their reign as European champions in style.