At about age 16 he graduated from primary school and moved to Phnom Penh to study medicine; this plan was apparently meant to please his parents when his true goal was to become a musician.

He initially worked in a Phnom Penh hospital as a nurse,[8] but was soon hired by the Cambodian national radio station as a singer with its band.

[1][2] While performing with the Cambodian national radio station, Sisamouth became a protege of Queen Sisowath Kossamak, mother of Head of State Norodom Sihanouk.

Initially, pop records from France and Latin America were imported into the country and became popular, inspiring a flourishing music scene based in Phnom Penh.

[17] Sisamouth is credited with launching the career of Ros Serey Sothea, who had been singing at weddings and later became the leading female singer in the Cambodian rock scene.

His son Sinn Chanchhaya believed that Sisamouth wrote roughly one song for every day that he was a professional musician, a period of nearly 20 years.

By the 1970s he was working regularly with lyricist Voy Ho,[21] and had adapted some traditional and popular Thai songs into his repertoire (for example, "Promden Jet" with Ros Serey Sothea).

Sinn Sisamouth disappeared during the Khmer Rouge genocide and his exact fate has never been confirmed, with multiple sources making contradictory claims.

Due to his ongoing popularity with the Cambodian people, there has been a great amount of speculation about his whereabouts after the Khmer Rouge forced the evacuation of all residents from Phnom Penh on April 17, 1975, and his apparent death at the hands of the new regime.

In the film Don't Think I've Forgotten, an interview subject speculates that Sisamouth was originally evacuated to a small village but was then ordered to return to the city to work for the Khmer Rouge in some capacity,[12] but it is unknown if he in fact followed this plan.

[12] Like many of his contemporaries, as a popular musician with Western influences, qualities widely known to be disdained by the Khmer Rouge, Sisamouth was likely to have been targeted for imprisonment or execution immediately.

[25] In 2006, Khmer Apsara magazine granted a long interview to a man named Keo Chamnab who claims to have seen Sisamouth's execution at a jail in Prek Ta Duong village in 1976.

Sisamouth looking very sad, told me that he was sent from Prek Eng, Kien Svay district, Kandal province, and he was jailed there for three days already.

Many of Sinn Sisamouth's master recordings were either destroyed by the Khmer Rouge regime in its efforts to eliminate foreign influences from Cambodian society,[11] or were lost due to decay.

[27] Western listeners were introduced to his work starting in the late 1990s with the release of the Cambodian Rocks bootleg album, followed by the soundtrack to the film City of Ghosts.

[13][29] Often called the "King of Khmer music," "the Cambodian Elvis," or the "golden voice," his lasting cultural impact is difficult to overstate.