Cruzeiro's victory put them top of the Brazilian championship on goal difference with 18 points from nine matches thanks to Internacional's 3-0 shock loss at lowly Nautico and Botafogo's 1-1 draw with Flamengo in their Rio derby.
Four days after winning the Libertadores Cup in a penalty shootout against Paraguay's Olimpia, Atletico rested all their leading players including captain Ronaldinho despite facing their most bitter rivals.
Atletico took the lead after 19 minutes with a penalty converted by Alecsandro before Cruzeiro took control with goals from midfielders Everton Ribeiro, Nilton and Ricardo Goulart, who scored two.
The Atletico fans made light of the defeat, partying throughout the match in celebration of their team's first title in South America's top club competition.
Title holders Fluminense lost 2-0 at Gremio, their fifth defeat in a row, and dropped into the relegation zone alongside ailing giants Sao Paulo.
Fluminense have gone 50 days without a win, since June 9, while Sao Paulo managed to end a run of seven defeats in all competitions with a 0-0 draw in their city derby against Corinthians at the Pacaembu.
Internacional began the day as leaders while Nautico were bottom but three late goals, one from new signing Maikon Leite, at the Arena Pernambuco World Cup stadium in Recife gave Nautico the upset win.
At the Maracana, Botafogo went ahead with a goal by Rafael Marques from Dutchman Clarence Seedorf's pass before midfielder Elias hit a last-gasp equaliser in the fourth minute of added time for Flamengo.