Rodrigo Rojo and Maximiliano Callorda scored either side of half-time for Fenix, as they moved three points clear of Wanderers at the top of the league standings, while third-placed Nacional lost 3-0 at River Plate to drop four points behind the leaders.
Fenix had been held to a 1-1 draw by Defensor Sporting in round four, which allowed Wanderers to join them on 10 points out in front in Uruguay.
Despite conceding possession to the home side for most of the match, Fenix were lethal when given the opportunity to shoot, with Rojo converting one of his side's three shots on target in the 17th minute, while substitute Callorda slotted another with eight minutes remaining.
Nacional's arch-rivals Penarol, who are set to play their game in hand on Wednesday, sit fourth with eight points from four matches after beating Apertura champions Danubio 2-0 on Saturday.
