Understanding pathways to environmental sustainability in tropical regions is a priority for conservation and development policies. Because drivers of environmental degradation often occur simultaneously a holistic approach is needed. We analyzed environmental degradation on demarcated indigenous lands in Guyana, using a spatially explicit, agent-based simulation model representing human livelihoods, forest dynamics, and animal metapopulations. We examined four plausible drivers of ecological degradation: conversion of land for agro-industrial use, erosion of hunting and dietary taboos, reduction in child mortality rates, and introduction of external food resources. Although social-ecological systems were resilient to internal changes, the introduction of external food resources resulted in large fluctuations in the system, leading to a deterioration in environmental sustainability. Our simulation model also revealed unexpected linkages within the system; for example, population growth rates of non-human animal species were related to the sustainability of human livelihoods. We highlight the value of simulation models as social-ecological experiments that can synthesize interdisciplinary knowledge bases and support policy development.