Nacional won 1-0 at Estudiantes thanks to Yulian Mejia's deflected strike in a vital Group Seven encounter to claim pole position in the standings with one matchday remaining.
The victory took Nacional to eight points, level with Libertad but ahead on goals scored, while Estudiantes (seven) dropped to third, three points clear of Barcelona.
Libertad had to come from behind at home to secure a 1-1 draw with Barcelona.
Nacional entered Thursday's match in Argentina having lost their past two games in the Colombian Primera A but managed to hold out against Estudiantes.
The hosts finished the game with 17 shots, including nine on target, to just four from Nacional but the Colombian visitors triumphed after Mejia surged through midfield in the 37th minute.
The 24-year-old's shot looped off an Estudiantes defender and over goalkeeper Hilario Navarro to settle in the net.
In Group Five, Boca Juniors notched a fifth consecutive win in the Copa Libertadores' group stage to continue their perfect campaign in South America's premier continental club competition.
Boca won 3-0 at Wanderers in Uruguay with Jonathan Calleri scoring a brace, while Fabian Monzon capped off the victory in the 74th minute with a goal from a direct free-kick.
The Argentine Primera Division club lead Group Five with 15 points, with Palestino and Wanderers level on seven in a battle for second spot.
Atletico Mineiro kept their hopes of qualifying for the round of 16 alive with a 2-0 triumph over Santa Fe.
The win took the 2013 champions from Brazil to six points from four games, third in Group One but only trailing Santa Fe on goals scored, while Colo Colo (nine) top the standings after their victory against Atlas (three points) on Tuesday.
