Christian Subero, Carlos Rivas and Jonathan Estrada helped Patriotas Boyaca to a comfortable 3-0 victory over 10-man Deportivo Pasto on Friday, while Deportes Tolima accounted for Uniautonoma 2-0 on Sunday.
Patriotas Boyaca stormed out of the blocks at the Estadio de La Independencia with two goals inside the opening three minutes from Subero and Rivas.
The result was put beyond doubt two minutes short of the hour-mark courtesy of Estrada before the visiting team were reduced to 10 men following Eder Ruales' second yellow card.
At the Estadio Manuel Murillo, Yulian Mejia converted a seventh-minute penalty and Davinson Monsalve scored 26 minutes later as Deportes Tolima started the season on a winning note.
Medellin were also triumphant in the opening round, upstaging defending champions Atletico Nacional 1-0 on Saturday.
Christian Marrugo was the hero, with his goal 16 minutes from time proving the difference at the Estadio Atanasio Girardot.
On a weekend that only featured 12 of the 18 teams, there were no draws.
First-half strikes from Jhonatan Agudelo and Omar Vasquez inspired Millonarios to a 2-0 win at home to Envigado.
There was late drama as Boyaca Chico edged Deportivo Cali 1-0 courtesy of Leonel Rios' 89th-minute winner.
Meanwhile, an own goal from Sergio Romero handed Once Caldas a 1-0 victory at Fortaleza.