Second-half goals from Ricardo Goulart and Marcelo Moreno lifted Cruzeiro to back-to-back wins at the Estadio Governador Magalhaes Pinto.
The victory sent Cruzeiro (13 points) to the summit after Internacional (12 points) were held to a second consecutive stalemate, this time drawing 1-1 at struggling Coritiba.
After a scoreless opening 45 minutes, the home side finally broke the deadlock just six minutes into the second half.
Goulart rose highest to nod home the opener - his third goal in two games having bagged a brace against Coritiba last week.
Marcelo Oliveira's men doubled their advantage and made sure of the three points 13 minutes from time, with Moreno's bullet header finding the top right-hand corner.
Cruzeiro (+4) are not alone at the top following Gremio's 2-1 win against Botafogo on Wednesday, which moved Gremio (+3) level on points but adrift on goal difference.
Gremio were forced to do it the hard way, however, after falling behind inside the opening six minutes.
Pablo Zeballos put Botafogo ahead in the sixth minute before Rodriguinho levelled proceeds on the stroke of half-time.
The hosts' completed their comeback with nine minutes remaining after substitute Maximiliano Rodriguez found the back of the net, having only been on the pitch for five minutes.
Fluminense are only one point off top spot after a four-goal second half saw them rout Sao Paulo 5-2 at the Estadio Jornalista Mario Filho on Wednesday.
Goals from Rogerio Ceni and Alexandre Pato had Sao Paulo 2-1 up at the break but that is as good as it got for the visiting team.
An own goal from Lucas restored parity just seven minutes after the interval before Walter added to his first-half strike to put Fluminense ahead.
And Wagner and Rafael Sobis both scored in the space of three minutes to complete the memorable comeback in Rio.
In other results, Corinthians are three games without a win following their 1-1 draw at home to Atletico PR.
Talisca scored in stoppage time as Bahia salvaged a point against Flamengo, while Criciuma climbed out of the relegation zone courtesy of a hard-fought 1-0 win over cellar-dwellers Chapecoense.
Fourth-placed Palmeiras edged Figueirense 1-0 courtesy of Henrique's 37th-minute goal and Santos coughed up two leads as they drew 2-2 with Goias.
Meanwhile, Atletico Mineiro withstood a late rally to beat Vitoria 3-2.
