ABSTRACT The Mesoamerican region is a center of domestication and high genetic diversity of Phaseolus vulgaris L., which continues to evolve on-farm as part of multi-cropping systems (milpa) and is commonly associated with maize. The genetic resources of the common bean provide knowledge of its agronomic potential. However, there is also a need to document the biochemical composition of the seed in the genetic resources preserved by Mesoamerican farmers. To assess the genotypic and environmental effects on the polyphenol, flavonoid and monomeric anthocyanin contents, and antioxidant activity (DPPH) in seed coats and cotyledons of the common bean, 54 native populations and five improved varieties were evaluated from seed samples that were cultivated in two cropping seasons under a randomized complete block design with four replicates. In addition, seed color parameters were evaluated. At harvest time, a dry sample of grain was obtained from each population, and after a soaking treatment of 12 h, seed coats were separated from cotyledons. The evaluated populations and varieties of common beans showed significant differences (P < 0.05) in polyphenol, flavonoid and anthocyanin compositions, antioxidant activity, and seed color parameters. The geographical origins of the populations and cropping season significantly affected the compositions of the seed coats and cotyledons, and the regions of origin and populations had significant interactions with the cropping season. Among populations, phenolic compound concentrations and antioxidant activities were higher in dark or pigmented seed coats than in the cotyledons. The genotype-environment interaction effects in bioactive compounds provide insights into options for genetic improvement of the common bean to promote their consumption.