Nani set Portugal on their way with a left-foot drive and further goals from Simao Sabrosa, Miguel Veloso and Edinho saw them clinch second place in Group One with 19 points, two points adrift of winners Denmark but one point ahead of Sweden.
The result completed the first stage of a qualifying comeback for Portugal, who had looked down and out at one stage after winning just one of their first five games.
"I'm very satisfied as winning this match means going forward in this marathon, in a group that in the end was one of the tightest in the fight for the top two places," Portugal coach Carlos Queiroz said.
They can now look forward to a two-legged playoff against one of the other second-placed teams, and with Portugal seeded they can expect that to be against Bosnia, Ukraine, Slovenia or Ireland, with the matches set for November 14 and 18.
"I think it's fair to say that it will probably be the unseeded teams that are right now more worried," said Queiroz, expressing no preference on the opponents.
With World Player of the Year Ronaldo out injured, Portugal relied on another of their wingers, Nani, to drive them forward.
Having had a thunderous shot blocked in the third minute, Nani opened the scoring 10 minutes later, collecting a pass from Deco just outside the box and giving the keeper no chance.
Malta were unable to build a single attack in the first half and a second goal looked inevitable, with Simao, Nani and Liedson all going close in the space of five minutes.
Just before half time, Simao secured the second goal. Deco's pass from midfield was deflected but still reached Simao, who curled it in.
Miguel Veloso added Portugal's third on 52 minutes with an easy tap-in from a Nani cross, and substitute Edinho completed the rout in the 90th minute by running on to a Simao through ball and rounding the keeper.
