He was the youngest of four siblings, with one brother and two sisters. His father was a prison warden in Battambang Province and was then a soldier during the Colonial Cambodia period. His father died of disease, and his mother remarried, and the union resulted in two more children.
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. He was also interested in Buddhist scripture and other books, as well as playing soccer and flying kites.
Around 1951, he passed elementary school and intended to study medicine in Phnom Penh, but continued working at becoming a singer and writing songs. Just as he had in elementary school, he became well known in his school for his music, and was asked to sing at school ceremonies.
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.