Ji-soo began his acting career by appearing in several theater productions and short films. In 2012, he landed cameo appearances in SBS’s To the Beautiful You and KBS2’s Family. His career breakthrough came in 2015 when he was cast in the MBC series Angry Mom, which earned him a Best New Actor nomination at the MBC Drama Awards. In 2016, he starred in the film One Way Trip, which gave him another Best New Actor nomination at the 37th Blue Dragon Film Awards. That same year, he acted alongside Kim So-hyun and Shin Jae-ha in the KBS2 drama special Page Turner, which scored him nominations for an Excellence Award and Best New Actor at the KBS Drama Awards. In 2017, he was nominated for Best New Actor at the 53rd Baeksang Arts Awards for his work in the hit JTBC series Strong Woman Do Bong-soon. In 2020, he received a Top Excellence Award nomination at the MBC Drama Awards for When I Was the Most Beautiful. Also in 2020, he was named Actor of the Year at the 25th Busan International Film Festival for Our Joyful Summer Days.

In 2021, Ji-soo faced a series of school bullying and sexual harassment allegations. In response, he posted a handwritten apology on his personal Instagram account. The scandal resulted in his removal from his ongoing KBS2 sageuk series River Where the Moon Rises. He later sued individuals who made false sexual accusations against him. He enlisted for his mandatory military service in October 2021.