William Ferreira's 70th-minute strike at the Estadio Leon was enough to hand the Bolivian outfit all three points.
Leon, a Liga MX club, sit second in the group, one shy of new leaders Bolivar. Emelec and Flamengo sit third and fourth but have a game in hand.
Velez Sarsfield are all but assured their spot in the knockout phase, after beating Atletico Paranaense 3-1 away from home in their Group One encounter.
The Argentine outfit had the benefit of playing against 10 men for much of the second half, and scored twice with their numerical advantage.
Agustin Allione opened the scoring for the visitors in Brazil, and their chances of holding on to win increased when Atletico went down to 10 as Fran Merida was dismissed on 51 minutes.
However, the home side would go on to score three minutes later to restore some hope, but Lucas Pratto reinstated Velez's lead before Hector Canteros topped off the scoring on 90 minutes.
The visitors had Emiliano Papa sent off late on, but it would not affect the result as Velez all but qualified for the last 16.
Newell's Old Boys went top of Group Six, with a 4-2 road win over Nacional in Uruguay.
Nacional led on 11 minutes at home when Juan Mascia scored, but Newell's would get the upper hand after Nicolas Castro and Marcos Caceres goals.
An Andre Scotti penalty on 61 minutes restored parity for Nacional, but the hosts would be decimated by dismissals shortly after.
Each of Rafael Garcia and Jorge Bava were sent off in the final 20 minutes, while David Trezeguet netted a late brace to ensure Newell's of the points.
Newell's are level on points with Brazilian outfit Gremio, who have a game in hand.
Argentine club Arsenal booked their last-16 place with a 3-1 win over Venezuelan outfit Deportivo Anzoategui.
Away in Puerto la Cruz, Arsenal got on the scoresheet via Matias Sanchez, Martin Rolle and Matias Zaldivia.
Deportivo Cali earned a very important 1-1 draw at home to O'Higgins, courtesy of a late equaliser to Nestor Camacho.
Camacho's goal deep into injury time saw the sides share the spoils in Santiago de Cali, to keep them ahead of their Group Three rivals.
O'Higgins - of Chile - remain one point behind Colombia's Cali, who sit second in the group, level on points with Cerro Porteno.
