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.
That means the top three are separated by just four points with El Nacional and Emelec set to meet again on Saturday.
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.
All four goals came in the first 30 minutes, Jonathan Gonzalez, Daniel Angulo and Henry Leon putting the home side comfortably ahead before John Garcia pulled one back for Quevedo.
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.
LDU Loja scored three for the second consecutive game when beating Manta 3-0, while Barcelona overcame Deportivo Quito 2-1.
