4 de Julho/PI 1-3 ABC Natal/RN *
| 03.10.2021 | ABC Natal/RN | 2-0 | 4 de Julho/PI | |
| 26.09.2021 | 4 de Julho/PI | 1-1 | ABC Natal/RN | |
*América/RN 5-2 Moto Clube/MA
| 03.10.2021 | Moto Clube/MA | 2-4 | América/RN | |
| 26.09.2021 | América/RN | 1-0 | Moto Clube/MA | |
Cianorte/PR 0-1 Aparecidense/GO *
| 02.10.2021 | Aparecidense/GO | 1-0 | Cianorte/PR | |
| 26.09.2021 | Cianorte/PR | 0-0 | Aparecidense/GO | |
*Atlético/CE 3-2 Paragominas FC/PA
| 03.10.2021 | Paragominas FC/PA | 2-1 | Atlético/CE | |
| 25.09.2021 | Atlético/CE | 2-0 | Paragominas FC/PA | |
*Campinense/PB 4-1 Guarany/CE
| 03.10.2021 | Guarany/CE | 0-2 | Campinense/PB | |
| 25.09.2021 | Campinense/PB | 2-1 | Guarany/CE | |
Esportivo/RS 2-3 Ferroviária/SP *
| 03.10.2021 | Ferroviária/SP | 1-1 | Esportivo/RS | |
| 25.09.2021 | Esportivo/RS | 1-2 | Ferroviária/SP | |
*Uberlândia/MG 2-2 Joinville/SC
| 02.10.2021 | Joinville/SC | 2-1/p.1-3 | Uberlândia/MG | |
| 26.09.2021 | Uberlândia/MG | 1-0 | Joinville/SC | |
*Caxias/RS 4-0 União Rondonópolis/MT
| 02.10.2021 | União Rondonópolis/MT | 0-2 | Caxias/RS | |
| 25.09.2021 | Caxias/RS | 2-0 | União Rondonópolis/MT | |