Seo In-gook participated in the first season of Mnet’s singing competition show Superstar K in 2009, where he emerged as the grand winner. That same year, he released his debut extended play Calling. The album’s same-title lead single earned him the Male Newcomer of the Year trophy at the 2009 Cyworld Digital Music Awards. In January 2014, he released his debut Japanese studio album Everlasting, which debuted at number nine on the Oricon Daily Chart.

Seo In-gook made his television acting debut in the 2012 KBS2 drama Love Rain, which won him Best New Actor at the 5th Korea Drama Awards. He next starred in the hit tvN series Answer Me 1997, which scored him a Best New Actor nomination at the 49th Baeksang Arts Awards. He and his co-star Jung Eun-ji also took home several Best OST trophies for the song All For You, which they recorded for the series. In 2013, he joined the main cast of SBS’s Master’s Sun, which gave him the New Star Award at the SBS Drama Awards. In 2014, he received another Best New Actor trophy at the KBS Drama Awards for the sageuk King’s Face. In 2015, he played a genius profiler in the KBS2 series I Remember You. In 2016, he was paired with Nam Ji-hyun in the MBC romantic comedy Shopping King Louis, which earned him an Excellence Award at the MBC Drama Awards. In 2021, he acted alongside Park Bo-young in tvN’s Doom at Your Service.

Seo In-gook revealed in an interview that he struggled with the eating disorder bulimia, which started when he was told during an audition to lose weight. In 2017, he enlisted for his mandatory military service but was eventually exempted after he was diagnosed with a bone and cartilage condition called osteochondritis dissecans.