Ahn Nae-sang made his screen debut in the 1994 short film Baeksekin (a.k.a. White Man) under the direction of Bong Joon-ho. In 2002, he appeared in the movie Public Enemy, which was both a critical and commercial success. In 2005, he acted a supporting role in the KBS2 revenge drama Resurrection, which recorded a peak viewership rating of 22.9 percent. In 2007, he starred in the SBS weekend series First Wives’ Club, in which he won an Excellence Award at the SBS Drama Awards. In 2009, he scored an Excellence Award nomination at the KBS Drama Awards for his performance in the top-rating drama Three Brothers. Originally slated for 50 episodes, the series was extended by 20 more due to its popularity. In 2011, he headlined the MBC sitcom High Kick 3: Counterattack of the Short Legs, in which he bagged the Popularity Award at the MBC Entertainment Awards. In 2014 and 2017, he picked up Golden Acting Awards at the MBC Drama Awards for Jang Bori Is Here and Golden Pouch, respectively. Also in 2017, he received an Excellence Award at the SBS Drama Awards for his work in Band of Sisters.

Ahn Nae-sang’s younger sister was formerly married to actor Sol Kyung-gu. Actress Yang Hye-ji is his niece.