Wanderers prevailed 3-2 over Juventud on Sunday to rise to the top of the Uruguay Primera Division, while Penarol's poor start continued.
Matias Santos and Sergio Blanco scored the decisive goals for Wanderers, who came from behind to win at Juventud's Estadio Municipal Parque Artigas.
The victory took Wanderers to 10 points from four rounds and saw the capital club claim top spot in the table, ahead of Fenix on goals scored.
Fenix were held to a 1-1 draw at home by Defensor Sporting on Sunday to end their perfect start to the season.
Wanderers took the lead in the fourth minute when Gaston Rodriguez beat Juventud goalkeeper Ignacio Barrios with a shot that deflected in off the post.
But having hit the front, Wanderers let the hosts back into the contest, giving the ball away twice in the lead-up to Juventud's 26th-minute equaliser.
A corner found defender Diego Rodriguez to take Juventud level, while the home side edged ahead eight minutes later when Jonathan Blanes scored from the spot after Jaime Baez had been fouled in the penalty area.
A red card to Juventud midfielder Rodrigo Viega just before half-time changed the game, however, with Wanderers overrunning the hosts after the break.
Santos equalised in the 67th minute, while Blanco took advantage of a defensive error to score the winner with 10 minutes remaining.
At the Estadio Centenario on Sunday, Penarol were denied their second win of the Clausura campaign after Racing held the 2012/13 champions to a 1-1 draw.
Penarol hit the front 10 minutes before half-time through Javier Toledo's header but a rapid counter-attack by Racing in the 71st minute ensured the visitors claimed a point.
Racing got the ball out to Cristian Tabo on the left flank and the 20-year-old released Luis Gorocito into the box before the striker finished from a tight angle.
The draw leaves Penarol in seventh position with five points from three games.
In other results on Sunday, River Plate won 1-0 at Liverpool and Cerro Largo defeated El Tanque Sisley 2-1.
Earlier in the weekend, Nacional slipped to third after being stunned 2-0 at home by Danubio, while Rentistas thrashed Cerro 4-1 and Sud America edged out Miramar Misiones 1-0.