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.
But Wanderers could not stay with Fenix on Saturday with the visitors sounding an early warning to the rest of the Uruguayan top tier.
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.
Fenix moved to 13 points from five matches and a goal difference of plus nine with Wanderers (10 points, plus five) in second.
On Sunday, Jonathan Ramirez, Martin Alaniz and Leandro Rodriguez all scored for River Plate in their comfortable win over Nacional, who lost their second straight match in the Clausura campaign to sit third with nine points.
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.
Defensor Sporting trumped Miramar Misiones 2-1 on Sunday, while Liverpool thrashed El Tanque Sisley 4-1.
In other results, Racing defeated Cerro 2-1, Juventud cruised to a 3-0 victory at Rentistas and Cerro Largo edged out Sud America 1-0.
