After winning eight of their last nine games, Cruzeiro faced a challenge as they hosted a Portuguesa side who had won their past three matches, including a 3-0 thumping of traditional Brazilian powerhouse Corinthians.
But it did not take long for the competition leaders to assert their authority on Wednesday with Cruzeiro attacking pair Everton Ribeiro and Borges both finding the net before 16 minutes had elapsed.
Willian added another in the 28th minute before Borges completed his double with a strike two minutes later to effectively seal the contest with a four-goal margin.
The victory allowed Cruzeiro to maintain their 11-point gap over second-placed Gremio, who secured a narrow 1-0 victory over Atletico PR courtesy of Cristian Riveros' goal on the stroke of half-time.
Brazilian international striker Jo hit a brace as Atletico Mineiro thumped Ponte Preta 4-0 to stay in the hunt for a continental position.
Mineiro are three points behind fourth-placed Atletico PR, who occupy the Copa Libertadores qualifying position, and are five points behind Botafogo, who are in the automatic qualification spot.
Ponte Preta also played an earlier match in the round, losing 2-1 at home to rock-bottom Nautico.
Sao Paulo slipped back into the relegation zone after a 3-0 defeat at 10-man Santos.
The home side were 1-0 up when Alison was sent off in the 43rd minute but still added two more goals to the score-line despite the disadvantage.
After finding themselves mired in the relegation zone, Sao Paulo managed to get their head above water but three losses in a row now see them fall back into the battle.
The team that leapfrogged Sao Paulo, Vasco da Gama, did so courtesy of a 3-1 home victory over Internacional.
It was Vasco's first win in seven matches.
In other results, Fluminese and Botafogo fought out a 1-1 draw, Vitoria shaded Goias 2-1, Corinthians won 2-0 against Bahia and Flamengo triumphed 2-0 at Coritiba.