Abstract Summary Studying biological systems generally relies on computational modeling and simulation, e.g., model-driven discovery and hypothesis testing. Progress in standardization efforts led to the development of interrelated file formats to exchange and reuse models in systems biology, such as SBML, the Simulation Experiment Description Markup Language (SED-ML) or the Open Modeling EXchange format. Conducting simulation experiments based on these formats requires efficient and reusable implementations to make them accessible to the broader scientific community and to ensure the reproducibility of the results. The Systems Biology Simulation Core Library (SBSCL) provides interpreters and solvers for these standards as a versatile open-source API in JavaTM. The library simulates even complex bio-models and supports deterministic Ordinary Differential Equations; Stochastic Differential Equations; constraint-based analyses; recent SBML and SED-ML versions; exchange of results, and visualization of in silico experiments; open modeling exchange formats (COMBINE archives); hierarchically structured models; and compatibility with standard testing systems, including the Systems Biology Test Suite and published models from the BioModels and BiGG databases. Availability and implementation SBSCL is freely available at https://draeger-lab.github.io/SBSCL/ and via Maven Central. Supplementary information Supplementary data are available at Bioinformatics online.