Compartment-specific degradation half-lives are essential pieces of information in the regulatory risk assessment of synthetic chemicals. However, their measurement according to regulatory testing guidelines is laborious and costly. Despite the obvious ecological and economic benefits of knowing environmental degradability as early as possible, its consideration in the early phases of rational chemical design is therefore challenging. Here, we explore the possibility to use half-lives determined in highly time- and work-efficient biotransformation experiments with activated sludge and mixtures of chemicals to predict soil half-lives from regulatory simulation studies. We experimentally determined half-lives for 52 structurally diverse agrochemical active ingredients in batch reactors with three concentrations of the same activated sludge. We then developed bi- and multivariate models for predicting half-lives in soil by regressing the experimentally determined half-lives in activated sludge against average soil half-lives of the same chemicals extracted from regulatory data. The models differed in how we accounted for sorption-related bioavailability differences in soil and activated sludge. The best-performing models exhibited good coefficients of determination (R2 of around 0.8) and low average errors (<factor of 3 in half-life predictions) and were robust in cross-validation. From a practical perspective, these results suggest that it may indeed be possible to read across from half-lives determined in highly efficient biotransformation experiments in activated sludge to soil half-lives, which are obtained from much more work- and resource-intense regulatory studies, and that these predictions are clearly superior to predictions based on the output of BIOWIN, a publicly available quantitative structure-biodegradation relationship (QSBR) model. From a theoretical perspective, these results suggest that soil and activated sludge microbial communities, although certainly different in terms of taxonomic composition, may be functionally similar with respect to the enzymatic transformation of environmentally relevant concentrations of a diverse range of chemical compounds.