Fernando Uribe and Wilder Guisao scored just either side of half-time to give Nacional a two-goal lead in front of their home crowd and although Quindio struck in the 59th minute through goalkeeper Julian Viafara, the hosts held on for their fifth straight league victory.
Nacional are top of the Primera A standings, four points clear of Millonarios, who were denied victory when Boyaca Chico struck in second-half injury time to claim a 1-1 draw.
In Medellin, Nacional hit the front in the third minute of first-half stoppage time when Uribe found space on the edge of the area and slotted the ball past Viafara.
It was 2-0 in the 54th minute when Guisao got on the end of a counter-attack, cut inside his defender and lifted his shot over Viafara but Quindio's goalkeeper gave the visitors some hope five minutes later when he curled a free-kick into the net.
Despite Viafara's first goal since 2011, Quindio could not manage an equaliser and Nacional held on for victory.
The win took Nacional to 19 points from seven games, while Millonarios (15 from eight), Santa Fe (14 from seven) and Deportivo Cali (14 from eight) are second, third and fourth respectively.
In Tunja, Millonarios looked on track for their fifth consecutive league win after Harrison Otalvaro's 67th-minute goal but a penalty in second-half stoppage time from Edwin Movil ensured Boyaca Chico claimed a point at home.
In other Primera A results from the weekend, Alianza Petrolere defeated Itagui 1-0 and Deportes Pasto drew 1-1 with Deportes Tolima.
