Flamengo were second best and Ronaldinho subdued in the first leg of the preliminary round tie, lucky to lose only by the narrowest of margins in the rarefied and cold air of the Victor Ugarte, at 4000 metres one of the world's highest stadiums.
The Brazilian side did manage to take the lead against the run of play when right-back Leonardo Moura ended a fine run on the right with a low cross to Luiz Antonio, who scored with half-an-hour gone.
Their advantage lasted two minutes, though, as defender Claudio Centurion headed the equaliser from a free-kick and midfielder Edgardo Brittes gave Potosi a deserved victory with another header 12 minutes into the second half.
Captain Ronaldinho almost did not travel to Bolivia with the squad last week over a pay dispute with Flamengo, who were crowned South American champions back in 1981.
Flamengo should put on a better show when they host Potosi in the return leg in Rio de Janeiro next Wednesday but anything short of a win will mean an embarrassing exit before the group phase.
Another of Brazil's leading teams, twice champions Internacional, beat 2004 winners Once Caldas of Colombia 1-0 at home in another of the six preliminary round ties.
Brazil striker Leandro Damiao scored the only goal when he took a superb through ball from Argentine playmaker Andres D'Alessandro and steered it past goalkeeper Luis Martinez.
Uruguay's Penarol, five times champions and runners-up to Santos last year, are another leading club having to earn the right to a place in the group phase.
They face Caracas FC of Venezuela in the first leg of their preliminary round tie in Montevideo on Thursday.
Chile's Union Espanola beat Mexican champions Tigres UANL 1-0 at home on Wednesday, while on Tuesday Argentina's Arsenal crushed Peruvian debutants Sport Huancayo 3-0 and El Nacional of Ecuador beat Paraguay's Libertad 1-0 in Quito.
