Only a crushing victory at the Centenario, in one of South America's 'clasicos', coupled with victory for either Chile or Ecuador when they clash in Santiago at the same time (2330 GMT), would secure qualification for next year's finals.
"Although there are still chances of qualifying in fourth place, the big objective, to be realistic, is the clash with Jordan in the playoff," said Lugano, after Uruguay's 1-0 defeat by Ecuador in Quito.
Even without Lionel Messi and Gonzalo Higuain, Argentina are clear favourites for another win, in one of the world's oldest international rivalries, that would prevent Uruguay claiming an automatic place in Brazil.
"We have evidently once again taken the longest road to qualify, but the most important thing in all this is to be at the World Cup," Lugano told El Pais, in an interview published on Sunday on the Uruguayan daily's sports website.
"Four years ago, we suffered in such a decider against Costa Rica and then had a great World Cup so all we want is to get to Brazil and it doesn't matter in what position nor on which day."
Qualifying via a playoff is a familiar route for Uruguay. They had to beat Costa Rica over two legs to qualify for the 2010 finals.
This time, with Argentina and Colombia already qualified, Ecuador, Chile and Uruguay are vying for the remaining two direct berths and November's two-legged playoff against Asia's Jordan.
Uruguay will be concerned not to pick up bookings against Argentina with 14 members of their squad on one yellow card and in danger of missing the playoff first leg if they collect another.
This group of players includes key players like striker Edinson Cavani, defender Maxi Pereira and midfielders Diego Perez, Cristian Rodriguez and Gaston Ramirez.
Argentina are expected to field the same second string attack that led them to a 3-1 win over Peru in Buenos Aires on Friday with Ezequiel Lavezzi, who scored twice, and Rodrigo Palacio joining Sergio Aguero in the front line.
Messi and Higuain, who between them have scored 19 of Argentina's 33 goals in 15 qualifiers, and midfielders Javier Mascherano and Fernando Gago were all ruled out of the final two qualifying rounds through injury.