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There are a variety of theories about what brought about the end of the Indus Valley civilization.

Impounding of the Indus (Raikes and Dales)

A large mud-extrusion caused by tectonic activity impounded the Indus causing collossal silting which gradually engulfed Mohenjodaro. Since it was a water-permeable barrier, only the silt level kept rising.

Climate changes
In modern-day India, rains occur in two seasons - monsoon and winter. Around 3000 BC, a similar climatic pattern would have been prevalent. However, further evidence suggests a stronger summer monsoon and warmer summers and cooler winters than at present.
Sea level changes
Invading Aryans
Earth movements

At around 2000 BC, land elevation occurred as a result of diastrophism (movement of the earth's crust) in the Indus delta district, causing the rivers to flood and the river flows to change.

As each city was closely linked to the river, the changes in the river flow had an extreme and negative impact on the cities' activities. Repeated flooding may have led to an accumulation of salt in the soil decreasing agricultural productivity.

The Ghagger Hakra River dried up and people were forced to abandon many of the cities such as Kalibangan and Banawali located along it's banks.

During the last years of Mohenjodaro, people started to reside in the citadel of the site instead of in the lower town, which suggests the formation of slums in these affluent cities. The control mechanism that had been managing the cities for hundreds of years was no longer functioning properly. However people continued to live in the cities.

Trade

Dependence on the trade with Mesopotamia, due to political turmoil in Mesopotamia towards the end of the 3rd millennium BC, trade and trading networks had collapsed. This trade collapse resulted in the disintegration of the huge and complex economic superstructure, i.e., manufacturing and marketing sectors and towns and cities.