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Irrigated agriculture plays a vital role in the economy of Pakistan by contributing about 90% of food production, 22% of GDP, employing about 45% of the overall labor force, and generating over 60% of foreign exchange. The role of water resources has become significant which underpins the food security in the country. Indus Basin Irrigation System (IBIS) is the lifeline for the economy of Pakistan and is the major pillar of food security. IBIS is one of the largest irrigation networks in the world and is confronted with multidimensional challenges out of which climate changes have attained paramount importance. The irrigation system was designed on a 67% irrigation system during the 19th century while the current cropping intensity has crossed the limits of 150-160% or even more. Continuous increase in population and consequently more food demands have shifted the pressure on the aquifer underlying the Indus Basin. India, USA & China, and Pakistan has become the 4th largest user of groundwater where about 40% of irrigated food production is dependent on groundwater. In Punjab province, about 1.2 million tubewells are extracting about 40-45 MAF of groundwater annually. Consequently, groundwater management has confronted a multitude of tiny users in Pakistan. Climatic changes have made the availability and reliability of surface water a question mark. Resultantly pressure on groundwater is increasing and water levels are dropping abruptly taking this resource beyond the bounds of rural poor farmers. The intrusion of saline water into the fresh aquifer, secondary salinity, and seawater intrusion are the major threats to groundwater quality. About 3000 piezometers have been installed to monitor groundwater behavior (levels and quality) in the Punjab province. A research study carried out in Lower Bari Doab Canal (LBDC) has indicated that by falling of water table from 40 to 70 ft. the cost of pumping per acre-feet of groundwater has increased by 125%. Similarly, it has been observed that in many urban areas groundwater is depleting at an annual alarming rate of 2.54 ft., (Lahore city) and the water table in sweet water zones in rural areas (Vehari District) has gone beyond 70-90 ft. Human activities like increasing cropping intensities, unplanned over pumpage, lack of awareness/capacity, use of chemicals in agriculture/food production, industrialization, urbanization, solid waste landfills, domestic effluents, lack of legal and regulatory framework, etc. are the major threats to sustainable use of groundwater for food security. Climatic changes are posing severe adverse impacts on the sustainable use of groundwater which is putting food security under threat. Global warming, rising sea levels, glacier melting, unprecedented rainfall, prolonged droughts, and floods are the consequences of changing climate which are affecting directly or indirectly the groundwater resources in the aquifer underlying the Indus Basin.