The Charruas - Copa America champions and World Cup semi-finalists - overcame Bolivia 4-2 in Montevideo on Friday in their opening qualifier, while Paraguay lost 2-0 against Peru in Lima.
But Lugano believes there is little between the South American rivals and has urged his players to be fully focused.
"We celebrated the win over Bolivia in the dressing room but immediately started to think of the Paraguay game," the 30-year-old Paris St Germain defender told Ovacion newspaper.
"Paraguay have always been a tough team to us. Football is quite even at the moment and each match is a different story. There are no difference between the teams.
"We have the opportunity to gain at least one point in Paraguay so we can be close to the top positions. I want this team to keep writing pages in history."
Paraguay forward Nelson Haedo-Valdez has called on the Guaranies to beat Uruguay in order to restore a calmness to their camp after Friday's loss in Peru.
"Uruguay are a powerful side in aerial play, but we also have players who jump well. We are focused on winning," Haedo-Valdez said at a press conference.
"The three points would be great to calm us down and consolidate ourselves as a team."
Chile will be looking to recover from a 4-1 defeat in Argentina when they face Peru, who will be aiming for a second straight win.
"This match is crucial," Chile midfielder Mauricio Pinilla said ahead of the game in Santiago. "We must gain the three points against Peru. There is no other possibility.
"We must be focused during the 90 minutes of the game. Peru are very confident, but we must to do the things we know."
Peru captain Claudio Pizarro has warned Chile how strong his squad are.
"We are not the fantastic four. We are the fantastic 28 in the squad," he said. "They may fear.
"We'll play our game, we'll do our job. Chile will not be the same as Paraguay. At home, they become stronger."
Bolivia boss Gustavo Quinteros believes his side cannot afford another defeat when they take on Colombia in La Paz.
"This is a must-win game," he said.
Colombia coach Leonel Alvarez admits playing at 3,600 metres above sea level may force the Cafeteros to play defensively.
"Other Colombian teams who tried to attack lost," he said. "We'll take some precautions. We want to get a result that helps us collect points on a difficult pitch, with difficult weather, high altitude."
Finally, Argentina travel to Venezuela to play the Vinotinto in Puerto La Cruz.
Tuesday's 2014 World Cup Qualifiers (CONMEBOL)
Bolivia vs Colombia
Chile vs Peru
Paraguay vs Uruguay