Catolica, who were beaten 2-1 by El Nacional in the previous game week, hit back positively - going three up within an hour through Diego Benitez, Jorge Cuesta and Andres Mendoza.
Andres Rios pulled a goal back but it was not enough to save Cuenca from a third defeat in five games as Jorge Celico's men moved three points clear at the summit.
Emelec, Catolica's nearest rivals, were beaten 2-0 by third-placed El Nacional thanks to goals from Edson Montano in either half.
At the bottom of the table, Deportivo Quevedo's search for a win goes on after they were beaten for the seventh time in 10 games - going down 3-1 to Independiente del Valle.
Macara were unable to pull further away from Juan Urquiza's men as they suffered a third defeat in a row, losing 3-1 to LDU Quito.
Edison Mendez and Gabriel Corozo put Quito in front and, while Michael Endara pulled one back, Gustavo Bou put to bed any fears of a comeback with a 90th-minute strike, securing Quito's first win in nine league matches.
