Conservation efforts and other land-management decisions are often intended to provide multiple benefits, but real or perceived trade-offs between goals can increase conflict and limit the practice of Multiple-Benefit Conservation. To support decision-making, policy, and management in the Sacramento–San Joaquin River Delta of California, where multiple potentially conflicting goals and values have been identified, we developed a flexible framework for quantifying the benefits and trade-offs that result from landscape change, implemented as an open-source R package. Integrating multiple data sets and methods, we developed metrics that represent (1) agricultural livelihoods, (2) water quality, (3) climate-change resilience, and (4) biodiversity support benefits and then projected the net effects on each metric of three alternative Delta landscapes. Each alternative represented changes that could result by 2050 from meeting habitat-restoration targets in the Delta Plan for riparian and non-tidal wetlands, the continued expansion of perennial crops, or a combination of the two. We found that habitat restoration would provide significant biodiversity support benefits and some climate-change resilience and water-quality benefits without significant trade-offs for agricultural livelihoods, while the continued expansion of perennial crops would provide significant benefits to agricultural livelihoods with simultaneous trade-offs to climate-change resilience and a mix of benefits and trade-offs for water-quality metrics. The combined alternative illustrated the interaction between restoration and perennial crop expansion, with still significant but reduced benefits to both agricultural livelihoods and biodiversity support. Our results provide insights into the effects of each of these drivers of landscape change, alone and in combination, with implications for policy and management to support the practice of Multiple-Benefit Conservation in the Sacramento–San Joaquin River Delta. Our framework serves as a foundation for future collaborative development among scientists, managers, policy-makers, and other interested parties to facilitate evaluation of a more comprehensive set of metrics across new alternative landscapes.