Lilongwe the capital city of Malawi has a population of 670,000 and is fast growing at a rate of 4.3% per annum. All streams and runoffs in the city drain in Lilongwe River, hence its water quality for human use appears to be deteriorating. This research was aimed at identifying the sources of pollution and assessing the quality of the water in Lilongwe River in terms of suitability for domestic purposes of cooking, bathing, washing and drinking. The section of Lilongwe River under study was chosen because there had been reports of water borne diseases occurring every rainy season, there were a lot of waste damping and river bank cultivation along the river despite the river being used for domestic purposes like drinking. The selection of sites for water sampling was done through a physical survey. The grab sampling method was used. Physical identification and interviews were done to identify the major sources of pollution in the study area. Analysis of the 14 chosen physical, chemical and biological parameters was done at the Government Central Water Laboratory in Lilongwe though some were analyzed at the site using portable meters. Analysis of the parameters followed the protocols of the APHA (1989) methods. The results of the socio-economic survey showed 197 activities that directly or indirectly polluted the water in Lilongwe River. The laboratory analysis results showed that the values of seven out of 14 analysed parameters were above the acceptable limits of the Malawi Bureau of Standards (MBS), concluding the occurrence of pollution in the river. These parameters were Lead (0.07±0.02 mg/l), Cadmium (0.14±0.08 mg/l), Phosphates (0.1±0.01 mg/l), Chemical Oxygen Demand (110±4.2 mg/l), Suspended Solids (81±6.2 mg/l), Turbidity (123±4 NTU), and Faecal Coliforms (3,781±300 counts/100ml). It is therefore concluded that the section of the river under study is polluted and not fit for domestic use. It is recommended that the water of Lilongwe River should not be used directly for domestic purposes of drinking within the study area. It is also recommended that an IWRM approach be used in order to solve the pollution problem of Lilongwe River.