Nam Joo-hyuk debuted as a model in 2013 before bagging his first acting role in the 10-episode tvN series Surplus Princess in 2014. In 2015, he starred in the KBS2 teen mystery drama Who Are You—School 2015, which won him Best New Actor at the 4th APAN Star Awards. In 2016, he landed his breakthrough role in the MBC series Weightlifting Fairy Kim Bok-ju, which earned him another Best New Actor trophy at the MBC Drama Awards. In 2018, he made his big screen debut in the historical film The Great Battle, which scored him several Best New Actor trophies, including one from the 39th Blue Dragon Film Awards. In 2019, he became part of the main cast of JTBC’s The Light in Your Eyes, which was nominated for Best Drama at the 55th Baeksang Arts Awards. In 2020, he led the hit tvN series Start-Up, which was hailed Outstanding Korean Drama at the 2021 Seoul International Drama Awards.

In April 2017, it was confirmed that Nam Joo-hyuk and his Weightlifting Fairy Kim Bok-ju leading lady Lee Sung-kyung were dating. The two have been close friends since their modeling days and also worked together in the tvN series Cheese in the Trap. However, the couple broke up only a few months later.