Captain Cristiano Ronaldo, Andre Silva, Bernardo Silva and Pedro Neto featured for the Portuguese, who missed goalkeeper Rui Patricio and Pepe.
Azerbaijan were put under pressure in the first ten minutes after a flying shot outside the area from Ruben Neves worked a save off Sahruddin Mehemmedeliyev who also denied Joao Cancelo.
Mehemmedeliyev remained busy ten minutes later as he advanced timeously from his area to smother a half-volley from Dominguez Duarte following a teasing ball from Ronaldo.
The latter's first chance towards the breakthrough came just two minutes thereafter when he headed a cross from the left-side towards the back-post over the top.
Portugal finally cracked the visitors albeit fortuitously ten minutes before halftime as a punch from Mehemmedeliyev bounced off Maksim Medvedev and into the net for an own-goal.
Fernando Santos threw on a substitution upon the restart, as Bruno Fernandes came on to replace Joao Moutinho on the side of the Portuguese.
Ronaldo came close to extend the home side's lead minutes from resumption with a powerful free-kick on the edge of the area, but it was deflected for a corner-kick.
Azerbaijan continued to see little of the ball midway through the second half, as Bernardo Silva charged clear to get a shot away from a surging run but Mehemmedeliyev smothered.
Nervous defending from Portugal with 20 minutes to go nearly let the visitors in, but Anatoliy Nuriyev ballooned a loose ball before Fernandes forced a flying save off Mehemmedeliyev.
Portugal leaned towards a strong finish in the final stages, but Mehemmedeliyev acrobatically denied Ronaldo from a free-kick and a snap-shot from Joao Felix, thus it ended 1-0.