The article analyzes the livelihood strategies of farmers to adapt to reduced amounts of water in the upstream Mekong Delta in Vietnam. The study was conducted in An Phu district, the upstream district of An Giang province, bordering Cambodia, the area first affected when the availability of water resource from the Mekong River changes. The study aims to learn about the impact of changes on livelihood patterns and agricultural livelihood strategies using qualitative and quantitative data collection methods including: household surveys, key informant interviews, participatory rural appraisal methods, and in-depth interviews with farmers. The results show that the decrease in water resources has led to transitions in the livelihoods of farmers. From 2011 to 2022, flood levels had changed, peak floods were lower, and duration of the seasonal floods was shorter. Farmers have gradually changed farming patterns and techniques and adopted different strategies, including from (1) rice to “safe rice” (44.73%); (2) rice to fruits (32.99%); (3) rice to vegetables (6.41%); (4) and vegetables to fruits (13.42%). The reason for these transitions are: reduced water resources availability for practical farming; higher profits are possible with alternative strategies; and, availability of new learning from neighbouring farmers. Better use of available water resources, protection of human health and the environment, and lower production costs are the pathways that farmers have been aiming to achieve effectively and safely on account of changes in their environmental conditions.