Porto will claim a 27th Primeira Liga title if they beat Pacos de Ferreira at the Estadio Capital do Movel on Sunday.
A 2-1 success over UEFA Europa League runners-up Benfica saw Porto take the lead in the race for the title but they could be overhauled if they fail to win.
Porto have yet to lose a game this season but face a difficult task against third-placed Pacos, who will play in next season's UEFA Champions League qualifiers.
Benfica, who lost their first league game against Porto, host relegation-threatened Moreirense at the Estadio de Luz.
They will look to put their 2-1 defeat to Chelsea in Wednesday's UEFA Europa League final behind them and capitalise on any slip-up by Porto to claim the league title.
Moreirense secured a 2-1 win over fellow strugglers Vitoria Setubal on Saturday to boost their hopes of survival.
Bottom club Beira-Mar face a difficult task to avoid relegation as they welcome Sporting Lisbon to the Estadio Municipal de Aveiro.
A 2-1 loss to Estoril severely hindered their survival hopes.
Olhanense and Gil Vicente host Maritimo and Estoril respectively as both sides look for the win that will secure their safety.
Both teams can still be relegated, as just three points separate 12th and 16th place.
Vitoria Setubal need a win to be absolutely sure of maintaining their top-flight status, but face a difficult task against Braga, who occupy a UEFA Europa League place.
Rounding off the fixtures, Vitoria Guimaraes host Rio Ave at the Estadio Dom Afonso Henriques, and Academica will travel to the Estadio da Madeira to face off against Nacional.