Ngee Ann Primary School has its roots in 1940. That year, the Ngee Ann Kongsi's Board of Directors which comprised the late Mr Lee Wee Nam, the late Mr Yeo Chan Boon, the late Mr Lim Kim Seng and a few other members set up a girls' school in a bungalow owned by a Kongsi member at River Valley Road, opposite what is now the AA building. It was named Ngee Ann Girls' School, the first Chinese girls’ school in Singapore. In 1967, it started accepting male pupils and refocused its activities to become a primary school.

In 1980, it took on its current name. In 1982, the school relocated to its current premises at Marine Parade.  It was officially opened on 30 March 1984 by the Marine Parade MP, Mr Goh Chok Tong, who was then the Minister of Defence and Second Minister for Health.