Oribe Peralta and Miguel Layun were both on the scoresheet as league-leading America won away from home at the Estadio Universitario de Nuevo Leon.
America have now claimed maximum points from their opening four games in the Apertura campaign to sit two points clear of Atlas at the summit.
Atlas - the only other unbeaten team in the league - were 1-0 winners at Pumas UNAM on Sunday.
Mexico international Peralta opened the scoring in San Nicolas de los Garza, flicking the ball through his opponent's legs before firing it past goalkeeper Nahuel Guzman in the 22nd minute.
Layun made sure of the win just past the hour-mark as he placed the ball beyond Guzman.
In other results, Queretaro came from behind to beat Santos Laguna 3-2 on Saturday.
Queretaro cancelled out Djaniny's 20th-minute opener with goals from Camilo Sanvezzo and Emilio Lopez before the interval.
Santos Laguna were back on level terms in the 65th minute but the visitors claimed victory thanks to Willian's strike three minutes from time as Queretaro rose to third in the standings - three points behind America.
Pachuca ended their run of back-to-back defeats, easing past Guadalajara 3-0 on Saturday.
Ariel Nahuelpan scored twice for Pachuca.
Chiapas also found the back of the net on three occasions as they overturned a two-goal deficit to beat defending champions Leon 3-2 on the same day.
Leon led 2-0 at half-time through goals from Carlos Pena and Mauro Boselli.
But Chiapas hit back with three unanswered goals in the second half courtesy of Bruno Pires, Emiliano Armenteros and Franco Arizala.
Elsewhere, Monterrey conceded two goals in the final 12 minutes as they lost 2-1 at Veracruz.
An own goal gifted Cruz Azul a 1-0 win over Puebla.
Second-bottom Morelia played out a goalless draw with fellow strugglers Tijuana.
Meanwhile, cellar-dwellers Universidad Guadalajara and Toluca failed to find the net in a scoreless stalemate.
