Yang Se-jong made his official TV debut in 2016 with a supporting role in the hit SBS series Romantic Doctor Teacher Kim. In 2017, he appeared in the SBS fusion sageuk Saimdang, Light’s Diary and in the OCN sci-fi thriller Duel. That same year, he starred in the SBS romance drama Temperature of Love, opposite Seo Hyun-jin. His work in the series won him multiple Best New Actor trophies, including one from the 54th Baeksang Arts Awards. In 2018, he acted alongside Shin Hye-sun and Ahn Hyo-seop in the SBS romantic comedy Thirty But Seventeen, which gave him an Excellence Award at the SBS Drama Awards. In 2019, he led the JTBC sageuk My Country: The New Age.

Yang Se-jong majored in theater and film at the Korea National University of the Arts. He enlisted for his mandatory military service in May 2020 and was discharged in November 2021.