Groundwater is the main source of irrigation for modern rice varieties in many countries including Bangladesh. However, this important resource is being over-exploited and depleted beyond natural replenishment of aquifers from rainfall and river flow. The aim of the study is to formulate policies by identifying key factors constraining sustainable use of groundwater for irrigation in the context of maintaining food security in the northwest Bangladesh. Both primary and secondary data considering environmental, social and economic aspects were used for assessing sustainability of groundwater use for irrigation. Analysis revealed a declining trend of groundwater table in the northwest Bangladesh during 1981–2014, where the most depleted groundwater table was in Rajshahi followed by Pabna, Bogra, Dinajpur, and Rangpur district. The magnitude of depletion of groundwater table in Rajshahi district was 4–12 m during 1981–2014. The major influencing factors for natural replenishment of aquifer such as, total annual rainfall significantly reduced by about 25.6% during 1981–2014; average annual river water levels slightly declined; wetland areas significantly reduced by about one-third; while the area irrigated for dry season rice (boro), the main driver of groundwater depletion, has increased about three folds during 1981–2014. Efficient irrigation management practices, such as low water demanding high value crops, volumetric water charging system, wet and dry irrigation system, etc. can be introduced widely to reduce excessive withdrawal of groundwater. Efficiency of existing water lifting devices including STW and DTW can be enhanced for increasing command area, and discouraged for new installation of tubewell. Bangladesh has recently experienced moderate rainfall during September-October. If the boro rice transplantation is completed by November, boro cultivation may benefit from late-monsoon rains and place less pressure on groundwater resources.