Seok-woo, a divorced workaholic fund manager, reluctantly agrees to take his young daughter, Soo-an, to Busan to see her mother as a birthday gift. They board the KTX train at Seoul Station along with various passengers including an expecting couple, Sang-hwa and Seong-kyeong, a high school baseball team, and others. Just as the train departs, an infected woman jumps aboard. Unnoticed by the crew, she quickly turns into a zombie and attacks a train attendant, setting off a domino effect of infection throughout the train.

Panic ensues as passengers realize that they are trapped with the rapidly spreading undead. Seok-woo struggles to protect Soo-an and teams up with Sang-hwa and others to fend off the zombies. The survivors are forced to make life-or-death decisions to ensure their own safety as the chaos leaks into each car. Amid the chaos, they discover that the infection has become a nationwide epidemic, and information about safe zones and the situation outside is scarce and confusing. As the train speeds towards Busan, the stronghold that has reportedly managed to hold off the virus, the passengers must unite and fight for survival against the hordes of relentless zombies.