Biodiversity is diminishing at alarming rates due to multiple anthropogenic drivers. To mitigate these drivers, their impacts must be quantified accurately and comparably across drivers. To enable that, we present a generally applicable framework introducing fundamental principles of ecological impact quantification, including the quantification of interactions between multiple drivers. The framework contrasts biodiversity variables in impacted against those in unimpacted or other reference situations, while accounting for their temporal dynamics through modelling. Properly accounting for temporal dynamics reduces biases in impact quantification and comparison. The framework addresses key questions around ecological impacts in global change science, namely, how to compare impacts under temporal dynamics across stressors, how to account for stressor interactions in such comparisons, and how to compare the success of management actions over time.