Lee Do-hyun landed his first mainstream acting role in the 2017 tvN series Smart Prison Living. In 2018, he became part of the SBS drama Thirty but Seventeen, which earned him a nomination for Character of the Year at the SBS Drama Awards. In 2019, he was cast in the hit tvN dark fantasy Hotel del Luna, which widened his popularity. In 2020, he bagged his first leading role in JTBC’s Eighteen Again, which was based on the 2009 American fantasy comedy film 17 Again. His work in the series won him several acting citations, including the Best New Actor for TV at the 57th Baeksang Arts Awards. That same year, he joined the Netflix horror apocalyptic series Sweet Home. In 2021, he led KBS2’s Youth of May and tvN’s Melancholia, opposite Go Min-si and Im Soo-jung, respectively.

In an interview, Lee Do-hyun expressed his love and care for his younger brother, who has a developmental disability. In 2023, it was revealed that he is dating his The Glory co-star Im Ji-yeon.