Corinthians made it three wins for Brazil while a bad night for Argentine sides was compounded by a first defeat for Velez Sarsfield.
Brazil striker Neymar netted a penalty and two brilliant second-half goals as holders Santos beat fellow Brazilian side Internacional 3-1 in Group One.
Santos, upset 2-1 by Bolivia's The Strongest at high altitude in La Paz three weeks ago, have three points from two matches. The Strongest lead the group with six points.
Neymar, Brazil's big hope for the 2014 World Cup, converted a penalty to give Santos a 1-0 half-time lead at their Vila Belmiro ground before exploding after the break.
In the 54th minute, he picked up the ball in his team's half and dribbled his way past three defenders before steering it past goalkeeper Muriel at close quarters.
Inter striker Leandro Damiao pulled one back 10 minutes later, but within two minutes Neymar had completed his treble, his speed on the ball leaving two defenders in his wake before he chipped over Muriel.
Fluminense beat Boca 2-1 to lead Group Four with a maximum six points, while Boca have only one from a disappointing 0-0 draw against weak Venezuelan side Zamora.
Argentine champions Boca, six times South American title winners, lost for the first time in 37 matches in all competitions.
BRILLIANT DECO
"We knew the pressure would be strong here and Boca tried to push us back into our half," man of the match Deco told Fox Sports.
"But we defended well when we had to and controlled the match, playing with quality and personality," added the former Barcelona, Chelsea and Portugal playmaker.
Fluminense took an early lead when Brazil striker Fred headed home a Deco free-kick flighted into the box in the 10th minute.
The goal, the first Boca goalkeeper Agustin Orion had conceded in eight matches in all competitions this year, stunned the home side and they took most of the first half to settle into their stride.
Visiting goalkeeper Cavalieri parried three stinging chances in quick succession in the last minute of the first half from defender Juan Insaurralde, striker Santiago Silva and playmaker Juan Roman Riquelme.
Boca, their tails up, equalised right after the break from a 47th minute free-kick taken by supreme specialist Riquelme.
The playmaker's curling kick hit the base of the post and came back into the middle off Cavalieri's back only for midfielder Leandro Somoza to rifle it home.
Fluminense were not to be deterred and eight minutes later Wellington turned Matias Caruzzo on the left and crossed low for Deco to shoot first time under Orion restoring the Brazilians' lead.
Corinthians beat Paraguay's Nacional comfortably 2-0 at home at the Pacaembu in Sao Paulo to notch up four points, two less than Group Six leaders Cruz Azul of Mexico.
Velez
