Understanding potential future influence of environmental, economic, and social drivers on land-use and sustainability is critical for guiding strategic decisions that can help nations adapt to change, anticipate opportunities, and cope with surprises. Using the Land-Use Trade-Offs (LUTO) model, we undertook a comprehensive, detailed, integrated, and quantitative scenario analysis of land-use and sustainability for Australia’s agricultural land from 2013–2050, under interacting global change and domestic policies, and considering key uncertainties. We assessed land use competition between multiple land-uses and assessed the sustainability of economic returns and ecosystem services at high spatial (1.1km grid cells) and temporal (annual) resolution. We found substantial potential for land-use transition from agriculture to carbon plantings, environmental plantings, and biofuels cropping under certain scenarios, with impacts on the sustainability of economic returns and ecosystem services including food/fibre production, emissions abatement, water resource use, biodiversity services, and energy production. However, the type, magnitude, timing, and location of land-use responses and their impacts were highly dependent on scenario parameter assumptions including global outlook and emissions abatement effort, domestic land-use policy settings, land-use change adoption behaviour, productivity growth, and capacity constraints. With strong global abatement incentives complemented by biodiversity-focussed domestic land-use policy, land-use responses can substantially increase and diversify economic returns to land and produce a much wider range of ecosystem services such as emissions abatement, biodiversity, and energy, without major impacts on agricultural production. However, better governance is needed for managing potentially significant water resource impacts. The results have wide-ranging implications for land-use and sustainability policy and governance at global and domestic scales and can inform strategic thinking and decision-making about land-use and sustainability in Australia. A comprehensive and freely available 26 GB data pack (http://doi.org/10.4225/08/5604A2E8A00CC) provides a unique resource for further research. As similarly nuanced transformational change is also possible elsewhere, our template for comprehensive, integrated, quantitative, and high resolution scenario analysis can support other nations in strategic thinking and decision-making to prepare for an uncertain future