Usman Khan is a right-handed batsman and a right-arm off-break bowler making his first-class debut for Rawalpindi in the 2017–18 Quaid-e-Azam Trophy on September 26, 2017.

In September 2018, Khan was named in Pakistan's Under-23 squad for the ACC Emerging Teams Asia Cup tournament. He accumulated 142 runs in the tournament, with his highest individual score being 65 runs against Bangladesh. Khan made his List A debut for Rawalpindi in the 2018–19 Pakistan Cup on March 13, 2019. In that match against Federal Areas.

On October 16, 2019, Khan made his Twenty20 debut for Rawalpindi in the 2019–20 National T20 Cup. During the tournament, he scored a total of 256 runs, with his highest individual score being 76 runs against Khyber Pakhtunkhwa.

In January 2020, Khan was selected in Pakistan's squad for the Under-19 Cricket World Cup. He played seven matches in the tournament.

Khan made his international debut for the Pakistan national cricket team on February 24, 2023. He played his first One Day International match against New Zealand in Karachi. In that match, he scored 71 runs off 82 balls, which was the highest score by a Pakistan batter on ODI debut against New Zealand. On March 4, 2023, Khan made his T20I debut for Pakistan against New Zealand in Lahore.

During the ODI series against New Zealand in 2023, Khan scored a total of 224 runs in 4 innings at an average of 74.66. His highest score in the series was 94 runs. In the same series, he also took 5 wickets with his off-spin bowling.

Based on his performances against New Zealand, Khan earned a call-up to Pakistan's Test squad for their home series against Sri Lanka in March 2023. Khan made his Test debut for Pakistan on March 26, 2023 against Sri Lanka in Galle. In Pakistan's first innings, he scored 75 runs.

In the second Test against Sri Lanka in Karachi, Khan scored 184 runs across both innings, including his maiden Test century of 108 runs in the first innings. His century made him the third Pakistan batter to score a Test hundred against Sri Lanka on home soil after Saeed Anwar and Younis Khan.

Following the Sri Lanka series, Khan was retained in Pakistan's Test squad for their tour of England in May-June 2023.

In the first Test against England at Lord's, Khan scored 50 runs in Pakistan's first innings total of 339. He also took 3 wickets in the match.

In the second innings of the same Test, Khan scored an unbeaten 109 runs off 183 balls to lead Pakistan's fightback, though the match ended in a draw. His century made him the first Pakistan batter since Younis Khan in 2016 to score a Test hundred at Lord's.

During Pakistan's subsequent ODI series in England in June 2023, Khan scored his maiden ODI century, an unbeaten 110 off 115 balls in the 2nd ODI at Lord's. At the conclusion of Pakistan's tour of England, Khan had accumulated 1101 runs across all formats in his first 5 months of international cricket.

His exploits in his debut international season earned him the Pakistan Cricket Board's International Cricketer of the Year award for the 2022-23 season.