Lyles started 2017 with his first senior national title in the 300 m at the 2017 USA Indoor Championships in the thin air of Albuquerque, New Mexico, improving the indoor world record by one hundredth of a second to 31.87 s. He earned a silver medal in the 4 × 200-meter relay with team USA at the 2017 World Relays. Lyles won two meets in the 2017 IAAF Diamond League circuit, winning the final ahead of American champion Ameer Webb and world champion Ramil Guliyev. However, injuries prevented him from competing much of the season and he missed the 2017 World Championships as a result.