Tropical rivers are known to support high biodiversity, and are often characterised by vast floodplain areas and seasonal inundation patterns (Dudgeon, 1992). These rivers are places for many important terrestrial and freshwater species such as three true river dolphins species (Platanista gangetica, Platanista minor and Lipotes vexillifer) and the facultative freshwater dolphin – the Irrawaddy dolphins (Orcaella brevirostris). The Mahakam River in East Kalimantan, Indonesia, is typical of other tropical rivers in Southeast Asia but is distinguished by a riverine population of the iconic Irrawaddy dolphins, known locally as Pesut. This freshwater population is classified as “Critically endangered” by the International Union for Conservation of Nature (IUCN). Like many other tropical rivers in Southeast Asia, the Mahakam River is also facing problems from rapid development in rural areas, characterised by a massive conversion of peatland forest to oil palm plantation, an increasing number of mining activities, and ongoing development of settlements. These developments are likely to have had both direct and indirect effects on the Irrawaddy dolphins. Water quality parameters and land use type from sites in the upper, middle, and lower sections of the Mahakam River were used to quantify relationships with between broadscale catchment land-use changes and river habitat changes while anthropogenic factors such as fishing pressure and other forms of human disturbance were also assessed in relation to dolphin distribution. The objectives of this analysis were to (i) quantify changes in water quality in relation to land use, (ii) investigate the key environmental factors associated with Irrawaddy dolphin distribution and abundance in the Mahakam River, and (iii) integrate these findings with other information on dolphin ecology to make recommendations that support dolphin conservation management. Over 1996–2017, the land use in the sub-catchments of government water quality monitoring sites demonstrated changes that reflected decreasing forestland and increasing estate cropland, mainly due to the development of the oil palm plantations in Indonesia. The downstream section of the river also received disturbance from a high proportion of agricultural and settlement land. These land-use changes were shown to be related to the state of water quality in the Mahakam River. Increasing TDS and SO4 were associated with increasing estate cropland and agricultural intensification, respectively, while decreasing COD and BOD concentration were related to changes in swampland area. The middle reach of the Mahakam River was indicated as the primary habitat for the Irrawaddy dolphins. Several land-use related water quality parameters appeared to influence dolphin distribution through indirect effects on prey distribution. However, other forms of human disturbances such as settlements and boat traffic likely had direct effects on dolphins, contributing to their absence from the lower reach of the river. Accordingly, conservation management of Irrawaddy dolphins in the Mahakam River should focus on factors influencing prey species productivity in the river, such as the formation of fish reserves.