Introduction: German chamomile is a botanical ingredient commonly used in cosmetics, thus determination of skin sensitization effects of German chamomile constituents is critical for the safety of consumers. Nonetheless, a systematic investigation of skin sensitization potential of chamomile constituents is lacking. Non-animal methods for skin sensitization hazard evaluation have been progressively accepted as attractive alternatives to conventional animal models, especially when used in an integrated fashion. Materials and Methods: In the present work, 30 constituents of German chamomile were investigated for skin sensitization using in silico, in chemico, and in vitro methods, including classification-quantitative structure-activity relationship (c-QSAR) models (ADMET predictor and CASE Ultra), an expert knowledge-based system (Derek Nexus), the Direct Peptide Reactivity Assay (DPRA), the high-throughput assay with dansylated cysteamine (HTS-DCYA), the KeratinoSens Ô assay, and the human Cell Line Activation Test (h-CLAT). Results and Discussion: Identical classification was found for 14 compounds upon comparison between computational and experimental methods. Seven compounds (umbelliferone, apigenin, kaempferol, isorhamnetin, nerol, a-terpinene, and carvone) were positive in both models, that is, in silico and experimental settings. Seven other compounds (caffeic acid, t-ferulic acid, cosemetin, hyperoside, a-terpineol, a-bisabolol, and chamazulene) were determined to be non-sensitizers instead. Conclusions: Among the compounds positive in experimental settings, umbelliferone and farnesene should be regarded as a potential concern because of their positive classification and significant concentration in German chamomile.