With the clock ticking over into added time, Penarol - Uruguay's most successful team with 49 titles - were seemingly on track to leave the Estadio Centenario in Montevideo with all three points after Antonio Pacheco scored a 59th-minute penalty.
But Uruguayan Primera Division league leaders Nacional, who had Santiago Romero sent off five minutes after Penarol defender Damian Macaluso was dismissed in the 79th minute - produced a stunning comeback to break the hearts of their fierce rivals, who sit fourth in the table.
Substitute Sebastian Fernandez equalised in the second minute of injury time and 38-year-old Uruguayan legend Alvaro Recoba came off the bench to win the game courtesy of a sublime free-kick four minutes later.
Nacional (33 points, +22) are within touching distance of winning the Apertura campaign, sitting seven points clear of Racing (26 points, +6) with three matches remaining.
Racing delayed Nacional's title celebrations for at least a fortnight - due to the international break - after they overcame El Tanque Sisley 3-1 on Saturday.
Daniel Acosta's first-half goal, and successful penalties from Mauricio Affonso and Juan Rodriguez cancelled out Joel Burgueno's opener.
River Plate climbed up to third with a come-from-behind 2-1 victory at home to Sud America.
Gaston Rodriguez's 75th-minute penalty gave Wanderers a 1-0 win against Juventud.
Danubio stunned Defensor Sporting 2-1 and Atenas chalked up a 2-1 victory over cellar-dwelling Tacuarembo.
Martin Sosa scored six minutes from time as Rentistas downed Fenix 1-0, while Cerro prevailed 2-1 at Rampla Juniors.
