In his early twenties, Kiernan visited Cambodia but left before the Khmer Rouge expelled all foreigners in 1975. Though he initially doubted the scale of genocide then being perpetrated in Democratic Kampuchea, he changed his mind in 1978 after beginning a series of interviews with several hundred refugees from Cambodia. He learnt the Khmer language, carried out research in Cambodia and among refugees abroad, and has since written many books on the topic.
From 1980 onwards, Kiernan worked with Gregory Stanton to bring the Khmer Rouge to international justice. He obtained his PhD from Monash University, Australia in 1983 under the supervision of David P. Chandler. He joined the Yale History Department in 1990, and founded the award-winning Cambodian Genocide Program at the Yale Center for International and Area Studies in 1994, and the comparative Genocide Studies Program in 1998. Kiernan currently teaches history courses on Southeast Asia, the Vietnam War and genocides through the ages.
In 1995 a Khmer Rouge court indicted, tried and sentenced Kiernan in-absentia for "prosecuting and terrorizing the Cambodian resistance patriots".