Regional connectivity is essential for gene flow and the movement of organisms to maintain connected networks of refugia, and to facilitate range shifts in response to climate change. Models of regional connectivity are typically based on pre-designated core areas for conservation, as was our model for Nature’s Network. However, alternative ecological priorities may not correspond with predetermined cores. Core-independent regional connectivity metrics, focused at the ecosystem-level, are needed to allow scientists and practitioners to define their own conservation priorities and then use regional connectivity to identify the best opportunities to link those alternative cores into conservation networks. A core-independent, regional connectivity approach also avoids boundary effects that occur when arbitrary cutoffs are used to define cores. We developed a suite of regional connectivity metrics that are not core dependent, but that are specific for broad categories of ecosystems. Our approach is based on “random low-cost paths” in a resistant landscape. Random low-cost paths are intermediate between deterministic least-cost paths and a random walk, generally following low-resistance routes, but exploring sub-optimal alternatives. The core-free versions of regional connectivity treat high ecological integrity points distributed in a fine grid across the landscape as potential sources and destinations for a large number of random low-cost paths, in effect estimating mid-range connectivity from every point to every neighbor within 5 km. We then used a graph-theoretic approach to estimate long-range regional connectivity (among all points in the selected ecosystem in 13 states ranging from Maine to Virginia) among these mid-range connectors. Long-range connectivity is then used to weight the point-to-point paths. The result was long-range regional connectivity based on the fine-scale features of the landscape. We intend to use this approach to regional connectivity in a process of scenario analysis to quickly assess the expected benefit on overall connectivity from removing resistance associated with a particular road segment (or road-stream crossing). The results will identify the most important road-stream crossings for regional connectivity in each target area, including combinations of multiple crossings that provide the largest increase in regional connectivity when upgraded together.