Atlético FC 0-4 Llaneros FC (COL) *
| 18.03.2021 | Llaneros FC (COL) | 4-0 | Atlético FC | |
| 10.03.2021 | Atlético FC | 0-0 | Llaneros FC (COL) | |
*Barranquilla FC 2-1 Deportes Quindío
| 17.03.2021 | Deportes Quindío | 0-1 | Barranquilla FC | |
| 11.03.2021 | Barranquilla FC | 1-1 | Deportes Quindío | |
*Boca Juniors Cali 2-1 Unión Magdalena
| 25.03.2021 | Unión Magdalena | 1-1 | Boca Juniors Cali | |
| 18.03.2021 | Boca Juniors Cali | 1-0 | Unión Magdalena | |
*Tigres FC (COL) 2-1 Bogotá FC
| 19.03.2021 | Bogotá FC | 0-2 | Tigres FC (COL) | |
| 11.03.2021 | Tigres FC (COL) | 0-1 | Bogotá FC | |
*Real Santander 3-2 Cortuluá
| 18.03.2021 | Cortuluá | 1-2 | Real Santander | |
| 11.03.2021 | Real Santander | 1-1 | Cortuluá | |
Fortaleza (COL) 1-2 Itagüí Leones FC *
| 17.03.2021 | Itagüí Leones FC | 2-1 | Fortaleza (COL) | |
| 11.03.2021 | Fortaleza (COL) | 0-0 | Itagüí Leones FC | |
Orsomarso SC 0-1 Valledupar FC *
| 17.03.2021 | Valledupar FC | 1-0 | Orsomarso SC | |
| 10.03.2021 | Orsomarso SC | 0-0 | Valledupar FC | |
*Real Cartagena 5-3 Atlético Huila
| 18.03.2021 | Atlético Huila | 2-3 | Real Cartagena | |
| 11.03.2021 | Real Cartagena | 2-1 | Atlético Huila | |