Reigning champions Santos lost the first game of their Copa Libertadores title defence as they went down 2-1 to The Strongest.
The 2011 winners were trying to consolidate their tag as favourites to win the title this year, but playing 3,600 metres above sea level in La Paz proved to be too big an ask.
Santos did go ahead in the 10th minute when Henrique tapped in after Daniel Vaca had failed to hold Paulo Henrique's free-kick.
But Paraguay striker Ernesto Cristaldo equalised 12 minutes before the break and, when Rodrigo Ramallo headed in Pablo Escobar's injury-time corner, the home side had the win.
Escobar felt his side were worthy of the win for stifling Santos' attack.
"When Neymar did not attack us, Ganso did, or Elano, or Borges did," he said. "The money Neymar makes in a month, we make it in eight months. You should spend a week here and a week at Santos to make a comparison."
The other Brazilian teams in action also failed to win.
Flamengo drew 1-1 with Argentina's Lanus on both teams' debut in Group Two. Seconds before the half-time whistle, Leo Moura put Flamengo ahead after a Junior Cesar cross from the left.
However, Cesar Carranza came off the bench for Mauricio Pereyra in the 73rd minute and equalised 60 seconds later. Silvio Romero crossed the ball and Mariano Pavone assisted Carranza to put the match even.
Leo Moura told Fox Sports that his team should have won the game, saying: "Even though earning a point as visitors is important, we had to win."
Finally in Venezuela, Corinthians got a 1-1 draw at Deportivo Tachira but did not produce anything close to their best.
The Venezuelan team took the lead in the 21st minute thanks to Sergio Herrera and were on course for a historic win over the Brazilian side. But defender Ralf levelled things up in the third minute of second-half injury time with a header.