Groundwater resources is the major source of potable water in Mchinji District of Central Malawi and globally. Although the total amount of water on and under the earth‟s surface is generally assumed to have remained constant, the rapid population boom coupled with extension of agricultural farmland and industrial development are putting pressure and stress on the quality and quantity of water resources. In principal therefore, „use and discard‟ philosophy in water resources cannot be subscribed (Lloyd, 1999). The situation ultimately calls for rational management of water resources to ensure its sustainability. Water intended for human consumption must be free from organisms that are the causative agents of diseases and must not contain chemical substances at concentrations that may be hazardous to human health. In addition drinking water should be aesthetically acceptable, free from unpleasant taste, color, odor and turbidity. Drinking water should also be free from bacteria and viruses whose presence would indicate fecal contamination. Some are known to be toxic and their concentrations must be below acceptable value, taking into account that drinking water is but one of the several pathways by which substances enters the body. ix Due to perceived concerns of over extraction and rapid water resources depletion, optimal management of groundwater resources are now receiving much attention. Their associated literatures have taken quite different approaches both philosophically and operationally to the analysis of how groundwater should be managed, allocated and cared for spatially and temporally. This study investigated the spatial and temporal fluctuations of concentrations of chemical and biological substances in groundwater such as pH, electrical conductivity, total dissolved solids, iron, fluoride, manganese, chloride, sulfates, sodium and fecal coliform in Mchinji District of Central Malawi. Through examination and analysis of static water levels as an indicator of water table fluctuations, groundwater availability was also measured. It was found that anthropogenic activities on the landscape can impact the quality and quantity of the water resources in this area and this impact on the various sectors of the inhabitant‟s livelihoods. Groundwater in Mchinji is composed of a number of chemical and biological elements whose origin is either from the material in which it percolates through, or stored before exploitation. Anthropogenic activities in this area plays a role in the quality and quantity of groundwater through land use and land cover change as evidenced by comparisons of Landsat Thematic x Mapper™ satellite images over different time scales. In Mchinji no regular groundwater monitoring is being done indicating a deficiency in sustainability interventions of the resource. This study calls for integrated and sustainable water resources management and coordinated efforts amongst water users, local councils, regulatory authorities and environmental policy makers. Of far greater importance in groundwater sustainability analysis is the issue of groundwater monitoring. It is imperative therefore to preserve the resource while preservation is still possible. Groundwater is now turning into „blue gold‟ and becoming a highly sought-after commodity. It should, however, be utilized sustainably to meet the needs of the present without compromising the ability of future generations to meet their own needs.