Mineiro lifted the Libertadores Cup for the first time in their history after beating Olimpia 4-3 in a penalty shootout on Wednesday.
But Mineiro, who were without the services of star playmaker Ronaldinho, suffered a hangover as they were soundly beaten by Marcelo Oliveira's men, who moved top of the Brazil Serie A.
Alecsandro had given Mineiro an 18th-minute lead from the penalty spot but that was as good as it got for the visitors, with a Ricardo Goulart brace and goals from Everton Ribeiro and Nilton completing the win.
Cruzeiro are level on points with Internacional, who were beaten 3-0 at Nautico, but occupy top spot on goal difference.
Elsewhere on Sunday, Botafogo dropped to third after they played out a 1-1 draw with Flamengo, while Coritiba could only manage a point following their 1-1 stalemate at home to Vitoria.
Strugglers Sao Paulo are still searching for their first win in over a month, with a goalless draw at Corinthians leaving the Brazilian giants without a victory in five games.
Gremio returned to the winners' list after accounting for Fluminense 2-0, while Bahia edged Goias 2-1 in their mid-table clash.
Meanwhile on Saturday, Vasco da Gama threw away a two-goal lead but did enough to beat Criciuma 3-2 for their second successive win, Atletico PR climbed out of the relegation zone thanks a 3-2 triumph at Portuguesa and Santos suffered a 1-0 defeat to Ponte Preta.
