Determining where biodiversity is likely to be most vulnerable to climate change and methods to reduce that vulnerability are necessary first steps to incorporate climate change into biodiversity management plans. Here, we use a spatial climate change vulnerability assessment to (1) map the potential vulnerability of terrestrial biodiversity to climate change in the northeastern United States and (2) provide guidance on how and where management actions for biodiversity could provide long-term benefits under climate change (i.e., climate-smart management considerations). Our model suggests that biodiversity will be most vulnerable in Delaware, Maryland, and the District of Columbia due to the combination of high climate change velocity, high landscape resistance, and high topoclimate homogeneity. Biodiversity is predicted to be least vulnerable in Vermont, Maine, and New Hampshire because large portions of these states have low landscape resistance, low climate change velocity, and low topoclimate homogeneity. Our spatial climate-smart management considerations suggest that: (1) high topoclimate diversity could moderate the effects of climate change across 50% of the region; (2) decreasing local landscape resistance in conjunction with other management actions could increase the benefit of those actions across 17% of the region; and (3) management actions across 24% of the region could provide long-term benefits by promoting short-term population persistence that provides a source population capable of moving in the future. The guidance and framework we provide here should allow conservation organizations to incorporate our climate-smart management considerations into management plans without drastically changing their approach to biodiversity conservation.