Considering Malta had taken just one point from nine previous matches in the qualifying campaign, it was the expected outcome, and now Portugal must look to maintain their momentum going into next month's double-header against another group runner-up.
The Portuguese have recovered well after a dismal first half of their bid to reach South Africa, and will surely now fancy their chances of reaching the finals, given they will be among the seeded teams in next Monday's draw.
Goals from Nani, Simao Sabrosa, Miguel Veloso and Edinho made it a comfortable evening for Carlos Queiroz's side in Guimaraes.
Manchester United midfielder Nani calmed any Portuguese nerves by scoring after 13 minutes. Veloso played the ball in from the left and Nani, just outside the 18-yard box, was quick to get his left-footed shot away, finding the bottom right corner.
Portugal were dominant and a second goal looked set to follow quickly, however it did not arrive until a minute before half-time when key man Simao, fresh from his starring role in the weekend win against Hungary, rammed home another shot from outside the penalty area.
Malta's only threat came in the 63rd minute, however Jamie Pace made a mess of his shot which almost hit the corner flag.
Portugal's third goal was a crisp finish from Veloso, as the left-back finished like a striker from around 12 yards after Liedson could not convert Nani's pass.
Coach Queiroz responded to the home crowd's cheers for Guimaraes midfielder Nuno Assis by bringing him off the bench for the final half-hour, in place of Raul Meireles.
Portugal did not need to push for further goals, knowing a victory was enough to secure second place in the group ahead of Sweden. However they still managed to find a fourth, as Edinho scored following a pass from Simao.