The intensity and frequency of droughts are projected to increase globally due to climate change. The Murray-Darling basin (MDB) is the largest river system in Australia and has been impacted by several multi-scale droughts during past decades. In this study, we studied the influence of drought and post-drought periods on the river water quality, using time series techniques and standardised drought index (SDI) values. Several water quality sites were selected for this study along the basin, representing headwaters to downstream regions of MDB. The main drought periods during the last four decades were identified using the calculated SDI index values by assigning a threshold value. The Millennium drought was the longest among the reported droughts and showed the highest severity index values. Nutrient loads were calculated for each site and categorised into drought, baseflow and post-drought periods based on SDI. The drought period showed the lowest median nutrient loads for all the sites with the lowest interquartile range (IQR), where the highest nutrient loads were reported during the post-drought period. These findings reveal that nutrients were retained in the landscape during the drought and released in higher loads during post-drought when the hydrology was activated after the rewetting. An approx. 1×10+3 to 1×10+5 kg day-1 increase in many nutrient loads were observed with distance downstream from headwater sites to lower Murray sites, especially after the Darling and Murrumbidgee River inflows. Correlation analysis revealed that post-drought peak flow was strongly correlated with (>0.8) with post-drought peak nutrient loads. TN, TP, And SRP followed an increasing trend during the low to moderate flows and then, at a certain level of flow, many nutrient concentrations started to decrease. These results suggest that hydrology is a key driver in controlling the water quality and more water quality deterioration can be expected in the future.