The defending champions overturned an early deficit to defeat Internacional 3-1 at the Estadio Francisco Stedile in Porto Alegre.
Ricardo Goulart, Willian and Marcelo Moreno were all on the scoresheet as Cruzeiro claimed their third successive win to move a point clear atop the table after seven rounds.
Cruzeiro are one point ahead of nearest rivals Fluminense, who earned a 1-0 victory over Bahia.
Marcelo Oliveira only made one change to the team that defeated Sport Recife on Wednesday, with Ceara coming in for defender Mayke.
And the rotation appeared to work against Cruzeiro during the opening 45 minutes as International hit the front before the half-time break.
Internacional engineered a way through Cruzeiro's defence in the 39th minute, with Andres D'Alessandro playing in Diogo Mateus, who squared the ball across the six-yard box for Wellington to tap in from close range against his former club.
But the visitors' restored parity two minutes before the interval thanks to Goulart, who scrambled quickest inside the penalty area to head home his fourth goal in three games.
Internacional were breached again following the break after Willian latched onto Everton Ribeiro's through ball to put Cruzeiro ahead with 20 minutes remaining.
And the league's leading scorer Moreno made sure of the points two minutes from time, converting a rebound after his initial effort was saved.
Elsewhere over the weekend, Corinthians routed nine-man Sport Recife 4-1 on Sunday.
Goals from Romarinho and Jadson had Corinthians 2-1 ahead at half-time and it all went downhill for Sport Recife after the break, with Durval and Neto Baiano both receiving their marching orders.
Jadson and Romarinho made the most of the numerical advantage, adding to their tallies as Corinthians ended a two-game winless run.
Goias climbed up to third in the standings, edging Figueirense 1-0 at the Estadio Orlando Scarpelli.
As for Gremio, they missed the chance to remain level at the summit after losing 1-0 at Sao Paulo.
In other results, Chapecoense moved off the foot of the table courtesy of a surprise 1-0 win over Palmeiras.
Santos played the final 19 minutes with 10 men but still managed to earn a share of the spoils at home to Flamengo.
Two goals in the space of two minutes lifted Atletico PR to a 2-0 triumph over Coritiba.
Dinei cancelled out Emerson Sheik's 43rd-minute opener as Vitoria drew 1-1 with Botafogo.
Meanwhile, Atletico Mineiro and Criciuma played out a goalless draw.
