The clash at Estadio Gran Parque Central was decided on spot-kicks after Wanderers and Danubio were level 2-2 on aggregate, which was the score at the end of extra-time on Sunday.
And in a match that saw both teams finish with nine men, Danubio prevailed on penalties to lift the trophy for the fourth time in their history following triumphs in 1988, 2004 and 2006-07.
Leonardo Ramos' men are level with Defensor Sporting in the all-time championship standings, though they are well behind powerhouses Penarol (38) and Nacional (33).
The Torneo Final was evenly poised heading to Montevideo after Danubio and Wanderers played out a goalless draw in the opening leg on Tuesday.
Uruguay's decider, pitting the Clausura champions against the Apertura winners, was always going to be a fierce contest with so much at stake in the return leg.
And Danubio made a dream start away from home, when Luis Sosa put the visitors ahead in the 25th minute.
Danubio went into the break leading by a solitary goal but they were dealt a major blow just eight minutes into the second half after defender Emiliano Velazquez saw red for a second bookable offence.
Wanderers were also reduced to 10 men when Gaston Bueno was dismissed with 20 minutes remaining.
Wanderers eventually found themselves back in the contest courtesy of Diego Riolfo, who levelled proceedings in the 78th minute.
With the match heading to extra-time, both teams were reduced to nine men as Javier Cabrera and Matias De los Santos were handed red cards.
Wanderers drew first blood in the opening extra-time period, taking the lead thanks to Nicolas Albarracin but the match was forced to penalties after Camilo Mayada restored parity in the 119th minute.
