Tuesday's hosts at the Estadio Centenario in Montevideo were being well-held by a Colombian side seemingly content with a scoreless draw, as it would have guaranteed them a spot in the World Cup finals.
But two goals three minutes apart to Edinson Cavani and Cristian Stuani sent the home fans wild and put the Uruguayans level on points with fourth-placed Ecuador in the South America qualifying group.
The top-four in the nine-country group advance automatically to Brazil, while fifth place must face Jordan, who qualified for the intercontinental play-off on Tuesday.
Uruguay are now six points clear of sixth-placed Venezuela, meaning they are virtually guaranteed of at least the playoff spot but will be hungrily chasing automatic qualification after their third straight victory in the group.
Jose Pekerman's Colombia remain in second spot on the table on 26 points, still ensconced in the top four although they missed the chance to make sure of their ticket to Brazil.
Colombia frustrated the hosts for large periods, as they played the ball around without any real desire to trouble the scorers.
So it was more relief than anything for the home fans when Cavani got on the end of a ball through from Maxi Pereira out on the right, to nod home the opening goal at the near post on 77 minutes.
The mood quickly changed from frustration to elation and just as they let their hair down, Uruguay made it a two-goal lead when second-half substitute Stuani stormed in to put away a blind-sighted cross from fellow sub Gaston Ramirez.
Uruguay manager Oscar Tabarez was undoubtedly pleased his bench players vindicated his decision to get them on the park, after a stalemate in the opening 45 minutes.
Colombia were the first team to have a sight on goal from a set piece, but Uruguay goalkeeper Fernando Muslera comfortably caught the incoming ball in the fourth minute.
The home side had their first chance from a dead-ball situation in the eighth minute but star attacker Luis Suarez could not bother Colombia's custodian David Ospina, as his shot from long range lacked power.
Colombian number 10 Teofilo Gutierrez had Muslera at full stretch moments later to parry a powerful strike and Uruguay failed to clear immediately, with the ball ricocheting around the area in an early danger sign for Tabarez's men.
Uruguay quickly got back on top, though, as their dominance was reflected through a number of corners prior to the interval, although they failed to look threatening from most of them.
Their best chance came when Andres Scotti rose highest at the back post in the 21st minute but Ospina managed to get a slight touch on the cross in, enough to see Scotti miss his header opportunity.
Uruguay came out fired up in the second half with Cavani declaring his intentions by hitting the post with a strike in the first minute after the interval.
Still, Colombia settled back into the game and were content with passing the ball around to burn valuable time as they chased a point to secure their spot in Brazil.
Uruguay persisted though and Suarez smashed a powerful volley from a lay-up header from Stuani just wide of the goal as the hosts looked dangerous.
Pereira then provided the ball that Uruguay had needed all game and Cavani did the rest to ease the tension in Montevideo.
Stuani's opportunism three minutes later was all Uruguay needed to seal three valuable points.
