Agricultural and hydropower developments in the upper of Mekong River have been significantly changing the flow. From 2012 to present, the appearance of drought and salinity, are raising concerns about water security in the delta. The article evaluated the changes of irregular flow changes on the mainstream of the Mekong River in both the flood and dry season. Results showed that before 2010, when the hydroelectric impact was not significant, the flow in 2000– big flood, at Chiang Saen station the highest flow was 3,192 m3/s while at Kratie station was 18,031 m3/s. In the drought year (1998) with only 8,612 m3/s in Kratie and 2,560 m3/s at Chiang Saen station was observed. Upstream drought appeared during March, while downstream it was common in April. During flood season, the largest monthly discharge at upstream stations usually occurred earlier than stations at downstream up to one month. The flood peak occurred during September at upstream while the flood peak occurred in downstream during October. After 2010, due to the influence of hydropower, the water level on the main stream has changed significantly. Especially large floods, no longer occurs in the watershed of Chiang Saen. Since many years the flood exceeds the alarm level is reduced in downstream. The study has proposed solutions to ensure water security in the delta.