Marcelo Gallardo's men made it six wins in seven league games with the victory in Buenos Aires.
Leonardo Pisculichi and Ariel Rojas struck in the first half before goals from Teofilo Gutierrez and Rodrigo Mora after the break.
It saw River move three points clear at the top, with Independiente sitting fourth.
Pisculichi opened the scoring in just the fourth minute when his free-kick from the right found its way through a crowded penalty area and into the bottom corner.
Rojas made it 2-0 eight minutes before the break, firing a stunning left-footed effort into the top corner from 25 yards.
Federico Mancuello gave the visitors hope with his 58th-minute header from a Jesus Mendez cross.
The in-form Gutierrez scored his seventh goal of the season for River soon after, intercepting a poor back pass before rounding goalkeeper Diego Rodriguez and netting.
Mora completed the win in style in the 78th minute, taking a Tomas Martinez pass before chipping Rodriguez.
Lanus sit second after a 2-0 win at bottom side Quilmes as Silvio Romero's penalty and Alejandro Cabral's own goal late in the first half saw them grab three points.
Newell's Old Boys are also three points adrift of top spot after a 1-1 draw at Racing Club.
Agustin Vuletich's 73rd-minute goal saw Olimpo past Belgrano 1-0 and San Lorenzo enjoyed a come-from-behind 3-1 win at Defensa y Justicia.
Jose Valencia's brace guided Rosario Central to a 3-1 win over Arsenal and Banfield struck a late equaliser to draw 1-1 at home to Boca Juniors.
Estudiantes drew 0-0 against Gimnasia La Plata, while the clash between Velez Sarsfield and Atletico Rafaela also finished goalless.
