The six goals were as many as Ecuador had scored in their previous 16 games against their neighbours.
Ecuador, who failed to qualify for the 2018 World Cup, scored four times in the first half only for a James Rodriguez penalty to cut the deficit just seconds before halftime.
Colombia, who were beaten 3-0 at home by Uruguay last week, struggled throughout and Gonzalo Plata restored Ecuador's four-goal advantage 12 minutes from fulltime only to be shown a second yellow card for his celebration.
Pervis Estupinan made it 6-1 in the final minute of the match to ensure a miserable day for Colombia.
Ecuador cemented their place among the early pacesetters in the South American qualifying group for Qatar 2022 with nine points from their first four games.
The top four teams in the 10-team South American group qualify automatically for the World Cup and the fifth-placed side goes into an inter-regional playoff.