The win, at the Estadio Pacaembu, means Muricy Ramalho's Santos gained little advantage ahead of the second leg next Wednesday at the Estadio Defensores del Chaco in Asuncion. In the 44th minute, Edu Dracena headed in a Neymar cross to gave Santos the lead, the ball hitting the crossbar before going in.
Only seconds later, Cerro Porteno could have levelled the scores but Santos keeper Rafael saved a Pedro Benitez header from a free-kick by Julio Dos Santos. In the final seconds of the game, Neymar crossed for Alan Patrick but his left-foot shot was saved with his feet by Cerro keeper Diego Barreto.
Dracena said: "It could have been 2-0, but another important point is that we did not concede goals tonight. We play better as visitors. I hope we can play better football in Paraguay in order to win. Tonight, we fought a lot, we showed an aggressive side," he told Fox Sports.
The other semi-final tie will see Uruguayan giants Penarol take on Argentinian league leaders Velez Sarsfield in the first leg in Montevideo on Thursday night.