| 2021-10-04 | Indian Wells Masters | Hard | R128 | 53 |  Kei Nishikori | 182 |  Joao Sousa (Q) | 6-7(5) 6-3 6-2 | H2H | 3 | 142 | 5 | 1 | 60.2% | 62.5% | 56.8% | 4/8 |
| 2021-09-18 | Davis Cup WG1 R1: POR vs ROU | Hard | RR | 250 |  Marius Copil | 150 | Joao Sousa | 6-3 2-6 6-4 | H2H | 3 | 104 | 10 | 3 | 61.3% | 69.6% | 65.5% | 0/2 |
| 2021-09-18 | Davis Cup WG1 R1: POR vs ROU | Hard | RR | 150 | Joao Sousa | 317 | Filip Cristian Jianu | 6-3 7-5 | H2H | 3 | 85 | 2 | 2 | 58.7% | 75.7% | 57.7% | 0/1 |
| 2021-07-24 | Tokyo Olympics | Hard | R64 | 145 |  Tomas Machac | 137 | Joao Sousa | 6-7(5) 6-4 6-4 | H2H | 3 | - | - | - | - | - | - | - |
| 2021-07-12 | Newport | Grass | R32 | 78 |  Tennys Sandgren (5) | 133 | Joao Sousa | 6-4 7-6(3) | H2H | 3 | 89 | 10 | 2 | 58.5% | 76.3% | 51.9% | 0/2 |
| 2021-06-28 | Wimbledon | Grass | R128 | 90 |  Andreas Seppi | 120 | Joao Sousa | 4-6 6-4 7-5 6-2 | H2H | 5 | 192 | 14 | 4 | 57.7% | 65.1% | 55.6% | 18/21 |
| 2021-05-31 | Roland Garros | Clay | R128 | 33 | Taylor Fritz (30) | 114 | Joao Sousa | 6-4 6-2 6-4 | H2H | 5 | 101 | 7 | 3 | 56.9% | 82.9% | 67.7% | 1/2 |
| 2021-05-17 | Lyon | Clay | R32 | 129 |  Kamil Majchrzak (Q) | 110 | Joao Sousa (Q) | 6-3 7-6(8) | H2H | 3 | 96 | 3 | 1 | 57.5% | 81.0% | 54.8% | 4/5 |
| 2021-04-26 | Estoril | Clay | R32 | 50 |  Cameron Norrie | 103 | Joao Sousa (WC) | 6-1 6-3 | H2H | 3 | 85 | 5 | 2 | 73.9% | 79.4% | 58.3% | 3/3 |
| 2021-04-19 | Serbia | Clay | R32 | 126 | Taro Daniel (LL) | 105 | Joao Sousa (LL) | 7-5 6-3 | H2H | 3 | 116 | 3 | 3 | 56.6% | 76.7% | 42.4% | 5/7 |
