He was born in August 23, 1932, in Stung Treng Province, the son of Sinn Leang and mother Seb Bunlei.
Sisamouth attended Central Province of Stung Treng Elementary School when he was five. At the age of six or seven, he started to show interest in the guitar, and he would be asked to perform at school functions.
By the time Cambodia was granted independence from France in 1953, Sisamouth's fine singing voice landed him a spot on national radio as a regular singer. He also continued his studies, working at Preah Ketomealea Hospital.
Because his presence and influence on Cambodian music was so great, he is still a household name and remains popular to this day in Cambodia.