The district was colonised in the second half of the 18th century by residents from Jaffna Peninsula, primarily from Alaveddy, Udupiddy and Navaly.

Mullaitivu District was under the control of rebel Liberation Tigers of Tamil Eelam for many years during the civil war.

The population of the district, like the rest of the north and east of Sri Lanka, has been heavily affected by the civil war.

[11] Several hundred thousand Sri Lankan Tamils, possibly as much as one million, emigrated to India or to the West during the war.

In 2016 the district was one of the poorest in Sri Lanka and had the second-highest incidence of extreme poverty according to the World Bank.

[16] Mullaitivu District has four local authorities all of which are Divisional Councils (Pradesha Sabhai or Pradeshiya Sabha).