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| 1st(1st leg) | El Nacional | - | Primero de Mayo | 3:0 (0:0) | ||
| 2nd (2nd leg) | Primero de Mayo | - | El Nacional | 0:1 | ||
| 1st(1st leg): 06/05/2022 23:00 | 2nd (2nd leg): 20/05/2022 21:30 | Winner: El Nacional | ||||
| 1st(1st leg) | Dunamis 04 | - | La Unión | 0:2 | ||
| 2nd (2nd leg) | La Unión | - | Dunamis 04 | 2:1 | ||
| 1st(1st leg): 07/05/2022 17:00 | 2nd (2nd leg): 22/05/2022 16:00 | Winner: La Unión | ||||
| 1st(1st leg) | Peñarol de Pallatanga | - | Unibolívar | 0:0 | ||
| 2nd (2nd leg) | Unibolívar | - | Peñarol de Pallatanga | 0:1 | ||
| 1st(1st leg): 07/05/2022 19:30 | 2nd (2nd leg): 28/05/2022 21:00 | Winner: Peñarol de Pallatanga | ||||
| 1st(1st leg) | Búhos ULVR | - | Aampetra | 0:0 | ||
| 2nd (2nd leg) | Aampetra | - | Búhos ULVR | 3:1 pso | ||
| 1st(1st leg): 07/05/2022 22:00 | 2nd (2nd leg): 13/06/2022 01:00 | Winner: Aampetra | ||||
| 1st(1st leg) | Imbabura | - | Orellanense | 3:0 | ||
| 2nd (2nd leg) | Orellanense | - | Imbabura | 2:4 | ||
| 1st(1st leg): 08/05/2022 01:00 | 2nd (2nd leg): 28/05/2022 18:30 | Winner: Imbabura | ||||
| 1st(1st leg) | Río Aguarico FC | - | Deportivo Santa Elena Sumpa | 1:0 | ||
| 2nd (2nd leg) | Deportivo Santa Elena Sumpa | - | Río Aguarico FC | 1:1 | ||
| 1st(1st leg): 08/05/2022 16:00 | 2nd (2nd leg): 27/05/2022 18:00 | Winner: Río Aguarico FC | ||||
| 1st(1st leg) | Chacaritas FC | - | Deportivo Santo Domingo | 1:1 | ||
| 2nd (2nd leg) | Deportivo Santo Domingo | - | Chacaritas FC | 1:3 | ||
| 1st(1st leg): 08/05/2022 18:30 | 2nd (2nd leg): 22/05/2022 21:00 | Winner: Chacaritas FC | ||||
| 1st(1st leg) | Manta | - | 7 de Febrero | 3:0 | ||
| 2nd (2nd leg) | 7 de Febrero | - | Manta | 0:0 | ||
| 1st(1st leg): 08/05/2022 21:00 | 2nd (2nd leg): 22/05/2022 18:30 | Winner: Manta | ||||
| 1st(1st leg) | Danubio | - | Portoviejo FC | 0:2 | ||
| 2nd (2nd leg) | Portoviejo FC | - | Danubio | 4:1 | ||
| 1st(1st leg): 13/05/2022 22:00 | 2nd (2nd leg): 21/05/2022 21:30 | Winner: Portoviejo FC | ||||
| 1st(1st leg) | Leones del Norte | - | Estudiantes de Cuenca | 4:0 | ||
| 2nd (2nd leg) | Estudiantes de Cuenca | - | Leones del Norte | 0:3 | ||
| 1st(1st leg): 14/05/2022 01:00 | 2nd (2nd leg): 21/05/2022 19:00 | Winner: Leones del Norte | ||||
| 1st(1st leg) | Samborondón | - | Universitario de Pillaro | 1:0 | ||
| 2nd (2nd leg) | Universitario de Pillaro | - | Samborondón | 0:0 | ||
| 1st(1st leg): 14/05/2022 20:00 | 2nd (2nd leg): 27/05/2022 22:00 | Winner: Samborondón | ||||
| 1st(1st leg) | América de Quito | - | FC Insutec | 0:0 | ||
| 2nd (2nd leg) | FC Insutec | - | América de Quito | 2:1 | ||
| 1st(1st leg): 14/05/2022 22:30 | 2nd (2nd leg): 29/05/2022 21:15 | Winner: FC Insutec | ||||
| 1st(1st leg) | Libertad de Loja | - | Bonita Banana | 0:0 | ||
| 2nd (2nd leg) | Bonita Banana | - | Libertad de Loja | 2:2 | ||
| 1st(1st leg): 15/05/2022 01:30 | 2nd (2nd leg): 29/05/2022 18:30 | Winner: Libertad de Loja | ||||
| 1st(1st leg) | Independiente Juniors | - | Independiente de Azogues | 1:0 | ||
| 2nd (2nd leg) | Independiente de Azogues | - | Independiente Juniors | 0:1 | ||
| 1st(1st leg): 15/05/2022 16:00 | 2nd (2nd leg): 29/05/2022 01:00 | Winner: Independiente Juniors | ||||
| 1st(1st leg) | Olmedo | - | Quito FC | 3:0 | ||
| 2nd (2nd leg) | Quito FC | - | Olmedo | 0:2 | ||
| 1st(1st leg): 15/05/2022 18:30 | 2nd (2nd leg): 29/05/2022 16:00 | Winner: Olmedo | ||||
| 1st(1st leg) | Atlético Santo Domingo | - | Vargas Torres | 1:1 | ||
| 2nd (2nd leg) | Vargas Torres | - | Atlético Santo Domingo | 3:0 | ||
| 1st(1st leg): 15/05/2022 21:00 | 2nd (2nd leg): 21/05/2022 16:00 | Winner: Vargas Torres | ||||
