Colombian Wilberto Cosme scored twice and Chile's Esteban Paredes added the third at the Olimpico in Mexico City to give Queretaro their first win of the new season after a defeat on the opening weekend.
Pumas had their Argentine forward Ariel Nahuelpan sent off after an hour for a dangerous foul on Dionicio Escalante.
Queretaro have a new team in the top flight after entrepreneur Amado Yanez bought up the franchise of the struggling Jaguars in the southern state of Chiapas and moved them to the city of Queretaro in central Mexico.
Champions America, who won the Clausura title at the end of last season, have yet to make a start. They have been allowed to postpone their first two matches because they had five players on international duty.
Their arch-rivals Guadalajara, who also postponed their opening match last weekend for similar reasons, scored an equaliser in added time for a 1-1 draw on Saturday away to the new Chiapas FC team formed with the franchise of the disbanded San Luis.
Promoted Veracruz upset 10-man Atlante 4-2 away in Cancun with Mexico winger Angel Reyna scoring a hat-trick.
Atlante had striker Alberto Garcia sent off in the 50th minute, three minutes after pulling his team level at 2-2.