Star striker Neymar ensured defending Copa Libertadores champions Santos finished top of Group One as they beat The Strongest 2-0.
The sought-after Brazil international turned the game Santos' way in the closing stages as he laid off the 86th-minute opener for Alan Kardec before sealing the win with a fine solo goal in the closing stages.
Neymar's late heroics broke the hearts of the Bolivians who had defended gamely as they sought to snatch a win that would have sent them through after Internacional lost 1-0 to Juan Aurich.
"The Bolivians defended during the entire match, sometimes they did it very hard," Santos manager Muricy Ramalho said. "But we never give up and we found our prize at the end. That's a sign that we are focused until the last minute.
"We will obviously try to repeat our title, but all the teams are very even. The true Copa Libertadores starts now."
Santos' win allowed compatriots Internacional to progress despite Luis Tejada netting a 14th-minute winner for Peruvian outfit Juan Aurich.
Inter will next face an all-Brazilian last-16 clash with Fluminense while Santos are again up against Bolivian opposition when they meet Bolivar.
In Group Eight, Universidad de Chile jumped ahead of Atletico Nacional to take top place with a 2-1 success over the Colombians.
Playmaker Matias Rodriguez opened the scoring for the hosts on 10 minutes, but Atletico equalised on 63 minutes when Copa Libertadores leading goalscorer Dorlan Pabon netted his seventh of the tournament.
But Osvaldo Gonzalez snatched the win with a powerful header six minutes later to set up a meeting with Deportivo Quito in the next round.
Atletico Nacional's defeat was soured further as they now face the difficult task of progressing past Velez Sarsfield.
Penarol defeated Godoy Cruz 4-2 in the other game in the group.
Nicolas Sanchez and Diego Sevillano had fired the Argentinian side 2-0 ahead but Penarol came roaring back after Jorge Zambrana scored the first of his two goals on 38 minutes.
The comeback was completed in the second half thanks to goals from Rodrigo Mora, Maximiliano Perez and Zambrana.