Guimaraes looked imperious from the start and they should have taken an early lead when Andre Andre headed a corner onto the crossbar in the eighth minute.
Hosts Belenenses received a boost to their chances in the 21st minute as Nii Plange received a straight red card for a strong tackle on Miguel Rosa.
But they were unable to make their numerical advantage tell and Guimaraes took the lead five minutes later.
Belenenses goalkeeper Matt Jones failed to hold on to an in-swinging corner and Andre nodded in from close range.
Their second arrived 12 minutes later, with Tomane guiding a glancing header past Jones after an inch-perfect cross from Hernani.
The visitors wrapped up the win just before the hour mark as Jones inexplicably palmed Alex's free-kick into his own goal, although it was the Guimaraes man's name that was added to the scoresheet.
Victory saw Rui Vitoria's men make it three wins from three matches to go top of the fledgling table - at least for the time being.
Sergio Conceicao continued his unbeaten start to life as Braga coach with a 2-1 triumph over Estoril - a match that will be remembered for a trio of memorable strikes.
Visitors Estoril, who have been drawn alongside PSV Eindhoven, Dinamo Moscow and Panathinaikos in this season's UEFA Europa League, have not started the season well.
Rio Ave thrashed them 5-1 in their own stadium on Sunday and they were unable to bounce back against Braga.
Pedro Santos put Braga ahead in the 34th minute with a moment of brilliance, as he cut in from the right and blasted an unstoppable effort into the top-left corner of the net.
Estoril restored parity just after the break in equally impressive fashion, with Emidio Rafael hammering a free-kick into the top-left corner from 30 yards.
Eder arguably saved the best goal until last, however, as the Portugal international brought down a cross on his chest, before producing an acrobatic scissor-kick to complete the win for Braga.