We performed a comprehensive and comparative phenotyping screening of the CC founder strains carried out at the German Mouse Clinic (GMC, www.mouseclinic.de). The Collaborative Cross (CC) is a large panel of mouse-inbred lines derived from eight founder strains, including three wild-derived strains (A/J, C57BL/6J, 129S1/SvlmJ, NOD/ShiLtJ, NZO/HILtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). The phenotyping analyses cover phenotypes related to human diseases such as behavioural and cardiovascular parameters, clinical chemistry, dysmorphology, bone and cartilage, energy metabolism, eye and vision, immunology, lung function, neurology, nociception, followed by a detailed pathological examination. For each strain, at least sixteen females and males were phenotyped leading to a highly robust data set. Metadata analysis showed that the three wild-derived strains are most different from the laboratory strains. For some parameters the wild-derived strains are more similar to each other than to the laboratory strains. NZO/HILtJ, A/J and 129S1/SvlmJ were most different from all other strains. The analysis of screen-specific parameter sets recapitulated the global tendency of phenotypic similarities between laboratory strains, but also detected phenotypes that distinguished single strain from all others. Our results confirmed already known strain characteristics but also identified new phenotypes. For instance reduced hearing sensitivity was described in A/J and NOD/ShiLtJ before but not for NZO/HILtJ. This data set will be a valuable baseline for understanding phenotype effects in CC strains.