<p>The previous comparative studies on watersheds were mostly based on the comparison of dispersive characteristics, which lacked systemicity and causality. We proposed a causal structure-based framework for basin comparison based on the Bayesian network (BN), and focus on the basin-scale water-energy-food-ecology (WEFE) nexuses. We applied it to the Syr Darya river basin (SDB) and the Amu Darya river basin (ADB) that caused the Aral Sea disaster. The causality of the nexuses was effectively compared and universality of this framework was discussed. In terms of changes of the nexuses, the sensitive factor for the water supplied to the Aral Sea changed from the agricultural development during the Soviet Union period to the disputes in the WEFE nexuses after the disintegration. The water-energy contradiction of SDB is more severe than that of ADB partly due to the higher upstream reservoir interception capacity. It further made management of the winter surplus water downstream of SDB more controversial. Due to this, the water-food-ecology conflict between downstream countries may escalate and turn into a long-term chronic problem. Reducing water inflow to depressions and improving the planting structure prove beneficial to the Aral Sea ecology and this effect of SDB is more significant. The construction of reservoirs on the Panj river of the upstream ADB should be cautious to avoid an intense water-energy conflict as SDB. It is also necessary to promote the water-saving drip irrigation and to strengthen the cooperation.</p>