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Rich resources and fragile ecosystems of estuaries are increasingly impacted by land use and land cover (LULC). However, previous studies of habitat quality (HQ) typically do not model the impact of LULC in Southeast Asian estuaries. Here, we used the Integrated Valuation of Environmental Services and Trade-offs (InVEST) model and the Patch-generating Land-Use Simulation (PLUS) model to assess and predict HQ and habitat degradation in the Johor River Estuary (JRE) from 1989 to 2047. Habitat quality contribution rate (HQCR) was used to quantify the impact of land-use changes on HQ. We analyzed the correlation and spatio-temporal changes in LULC and HQ, respectively. Our forecasts show (1) Construction land expanding more than 10 times from 1989 to 2047. (2) HQ increases slightly followed by a continuous decrease in the habitat quality index (HQI). (3) Degradation of HQI was from forests, agricultural land, residential land expansion and land reclamation. (4) Population growth, economic development, and national development policies may pose significant future threats to water, land, and marine traffic in the Johor River. Our results show that land-use changes affect HQ and future development of the JRE should integrate the impacts of natural and human factors on LULC changes.