Brazil striker Adriano scored a hat-trick in a 5-0 win over Chile on Sunday to guarantee the world champions a place at next year's finals in Germany while Marcelo Zalayeta emulated him to give Uruguay a dramatic 3-2 win over Colombia.
Brazil's win means they keep up their record as the only country to have played at every World Cup finals while Uruguay's victory lifted them into the fifth-place play-off position in the 10-nation South American group.
Uruguay's win also helped Ecuador and Paraguay, third and fourth respectively.
Ecuador need only a draw at home to Uruguay next month to qualify while a win in Venezuela will be enough for Paraguay to book their place with one game to spare.
After 16 rounds of the marathon contest, Argentina, who qualified last June and lost 1-0 to Paraguay on Saturday, lead with 31 points followed by Brazil on 30.
Ecuador have 26 after their 2-1 win in Bolivia on Saturday and Paraguay are one point behind after their first win over Argentina in a World Cup qualifier.
The top four teams qualify directly for Germany while the fifth spot, occupied by Uruguay on 21 points, earns a play-off over two legs against the Oceania region winners, almost certainly Australia.
Colombia and Chile, on 20 points, could still finish fifth and Venezuela, who have 18 points, also have an outside chance, although their final match is away to Brazil.
Colombia host Chile in October and then visit Paraguay three days later. The Chileans, meanwhile, finish their programme at home to Ecuador.
Brazil, who became the first defending champions forced to qualify for the subsequent tournament under a new FIFA ruling, raced to a four-goal lead in less than half an hour against bemused opponents.
Central defender Juan made the breakthrough after 11 minutes with a close-range header from a corner and Robinho added the second 11 minutes later as he finished off a sweeping move which went from one end of the field to the other.
Adriano then added two more goals in a three-minute spell, the first a low shot into the far corner from Robinho's pass in the 27th minute and the second a header from a corner.
The Inter Milan player completed his hat-trick in injury time.
"The important thing was that we qualified," said Adriano, who is still fighting for a regular place in the team.
"I hope to continue like this and slowly but surely I'll get there."
His striking partner Ronaldo, who went off at halftime complaining of muscular discomfort, completed his sixth international without scoring.
In stark contrast to the festive atmosphere in Brasilia, Colombia faced a rowdy, hostile 60,000 crowd at Centenario stadium in Montevideo, venue for the first World Cup final in 1930.
Zalayeta headed Uruguay in front from Alvaro Recoba's cross two minutes before halftime and put the Sky Blues in a commanding position when he fired the second past Miguel Calero six minutes into the second half.
But with 12 minutes to go and Uruguay apparently coasting, Colombia fought back.
Elkin Soto reduced the arrears with a fulminating 25-metre shot from Angel's neat layoff in the 79th minute. Two minutes later, Soto returned the compliment by bursting to the byline and providing the cross for the Aston Villa striker to head the equaliser.
With the stadium silent and Uruguay coach Jorge Fossati disconsolate on the touchline, Uruguay found a winner with four minutes to go.
Fabian Estoyanoff's cross from the right eluded the Colombia defence and found Zalayeta lurking at the far post, leaving him with the easy job of tapping into the empty net.