Main
Ju Ji-hoon as Lee Chang, the Crown Prince of Joseon and heir presumptive to the throne. Although he is the King's only child, his late mother was unmarried, meaning that a son born to the queen consort would become the heir apparent and new crown prince. Suspicious of the illness afflicting the King, and his recent lack of public appearances, his investigation not only uncovers a dangerous epidemic that brings the dead back to life, but also a plot to betray the royal family and usurp him as heir.
Bae Doona as Seo-bi, a physician from Dongnae, and one of the only two survivors of the plague's original outbreak. She desperately seeks to find a cure and comes to possess a journal containing crucial information about the disease.
Ryu Seung-ryong as Lord Cho Hak-ju (seasons 1–2), the Chief State Councilor of Joseon, who is the head of the Haewon Cho clan and Lee Chang's political rival. He is the father of Queen Consort Cho and Cho Beom-il, and the uncle of Cho Beom-pal. A cold, ruthless leader, he is desperate to secure his power over the throne through Queen Cho's unborn child, whom he seeks to make heir to the throne in place of Lee Chang.
Kim Sung-kyu as Yeong-shin, a mysterious tiger hunter from the South who is the only survivor of the first outbreak. A strong fighter, uniquely skilled with a novel bird gun (Joseon matchlock musket), and who shares little of his past, he allies himself with Lee Chang and helps lead the fight against the undead.
Jeon Seok-ho as Cho Beom-pal, a magistrate of Dongnae and Cho Hak-ju's nephew, shown to have somewhat of a good nature but to be incompetent and easily scared.
Kim Hye-jun as Queen Consort Cho (seasons 1–2), the young and pregnant queen of Joseon, and the King's primary consort. She is Cho Hak-ju's daughter, Cho Beom-il's sister and Lee Chang's stepmother. Like her father, she is desperate to secure her power over the throne by giving birth to a son who will displace Crown Prince Lee Chang as the rightful heir.
Kim Sang-ho as Mu-yeong (seasons 1–2), Prince Chang's loyal personal bodyguard who accompanies him to the southern provinces to investigate the king's illness, leaving his pregnant wife in the capital.
Huh Joon-ho as Lord Ahn Hyeon (regular season 1; recurring season 2), a former governor considered a war hero for his part in the Imjin War. Despite his popularity with the people, he retired from public service to live a quiet life in Sangju. He was also a mentor to the young Lee Chang.
Jun Ji-hyun as Ashin (guest season 2; main in special), a mysterious woman from Hamgyong Province in the far north of the country.
Kim Si-a as young Ashin (special)
Park Byung-eun as Min Chi-rok (recurring season 2; main in special), head of the Royal Commandery and a skilled archer who becomes suspicious of the Queen.
Koo Kyo-hwan as Ai Da Gan (special), the Leader of the nomadic Pajeowi tribe of the Jurchen people
Kim Roi-ha as Ta Hab (special), Ashin's father and head of the Northern Seongjeoyain tribe of the Jurchens
