Having led 2-0 and 4-1, Nacional held on for a 4-3 victory over Fortaleza, who dropped to the bottom of the table thanks to the loss, despite conceding twice in the final 10 minutes.
George Saunders and Argemiro Vacca struck late for Fortaleza but it was not enough for the visitors, who remain winless in their past three matches.
Nacional's win took them three points clear of Millonarios (30 points) at the top of the Primera A standings after the latter suffered a shock loss on Saturday at lowly Uniautonoma, who leapfrogged Fortaleza.
In Medellin on Sunday, Nacional opened the scoring just after the quarter-hour mark in front of their home fans when Edwin Cardona's free-kick found the back of the net after bouncing in front of Fortaleza goalkeeper Andres Mosquera.
The hosts led 2-0 in the 26th minute with Santiago Trellez stabbing his shot into the roof of the net after a cutback from Cardona.
The match exploded in the final half hour with Jorge Ramos putting Fortaleza on the scoreboard with a nice finish from Vacca's through ball in the 65th minute before Nacional struck twice in quick succession.
Luis Paez struck in the 73rd minute for the league leaders, following good lead-up work by Jairo Palomino, while Cardona set up Nacional's fourth goal, which was scored by Fernando Uribe five minutes later.
Just as Nacional looked comfortable though, Fortaleza responded again with Saunders scoring from a corner in the 80th minute before Alexander Jaramillo teed up Vacca with three minutes remaining.
The visitors could not find an equaliser, however, and Nacional held on for a crucial win.
On Saturday in Barranquilla, Uniautonoma forward Cristian Fernandes Mejia struck in the 50th minute to stun visiting Millonarios and end his team's five-game losing streak.
Uniautonoma rose to 17th with 15 points, while Fortaleza (14 points) now prop up the table.
Junior, who sit third, could have jumped above Millonarios after that result but had already lost 3-0 at fifth-placed Once Caldas.
Fourth-placed Santa Fe defeated Atletico Huila 2-1 to move within a point of Millonarios and Junior in the table, while La Equidad, who occupy sixth spot, overcame Medellin by the same scoreline.
In other results, Itagui won 2-1 at Deportivo Pasto, Boyaca Chico crushed derby rivals Patriotas Boyaca 3-0, Alianza Petrolera triumphed 2-1 against Deportes Tolima and Envigado defeated Deportivo Cali 3-1.
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