Neymar ensures Santos' passage to last 16
Santos, inspired by the talismanic Neymar, defeated The Strongest 2-0 at home to exact revenge on the side who beat them in the rarefied air of the Bolivian capital two months ago when they began the defence of their title.
However, they must now return to La Paz's 3,600 metre altitude in a first knockout round that also pits twice champions Internacional against 2008 runners-up Fluminense in an all-Brazilian tie next month.
Santos, three times South American champions, scored twice in the final four minutes, Neymar laying on the first with a cross to substitute striker Alan Kardec, whose header beat goalkeeper Daniel Vaca.
Less than two minutes later, Neymar broke through the defence to steer the ball past Vaca and secure Santos's meeting with Bolivar, who will be at home for the first leg at Bolivia's national Hernando Siles stadium in two weeks from now.
Internacional, champions in 2006 and 2010, qualified in second place in the group despite a disappointing performance in a 1-0 defeat away to Juan Aurich of Peru.
The Strongest needed to beat Santos to have any chance of qualifying in Inter's place.
Panama striker Luis Tejada scored the only goal when he headed Juan Aurich's winner after a quarter-of-an-hour in the Peruvian champions' home town of Chiclayo.
Copa Sudamericana holders Universidad de Chile, who won South America's equivalent to the Europa League in December, beat Atletico Nacional to snatch top spot in Group Eight from the Colombians and will meet Deportivo Quito of Ecuador.
In a high tempo clash between the top two teams in the highest-scoring group at Chile's national stadium in Santiago, Argentine winger Matias Rodriguez put "La U" ahead with low drive from the edge of the box in the first half.
Striker Dorlan Pabon, the group stage's top scorer with seven goals, equalised just past the hour with a rising shot from the right but man-of-the-match Osvaldo Gonzalez restored the Chileans' lead with a header five minutes later.
"We've shown that we've been improving with each match," said Gonzalez, whose side lost away to Atletico Nacional in their opening group match before picking up 13 points from their next five.
"Now the real Libertadores starts, with home and away knockout ties which is totally different," he told Fox Sports.
Atletico Nacional go into the only clash between former champions, the 1989 winners qualifying for a tie with Velez Sarsfield of Argentina, who won the title in 1994.
Also among six former champions in the last 16 are Boca Juniors (six titles), who face Union Espanola of Chile, with the first leg at their Bombonera cauldron in Buenos Aires, and 1998 winners Vasco da Gama, who meet Lanus of Argentina.
Corinthians, one of Brazil's biggest clubs still looking to win the continental title for a first time, face surprise qualifiers Emelec of Ecuador and Paraguay's Libertad meet Cruz Azul of Mexico.