The Mesoamerican region is center of origin, domestication, and diversification of maize. In this ecogeographic context, the objective was to evaluate the variation in the phenolic compounds, antioxidant activity and concentration of minerals in the grain of a population collection of yellow maize landraces from southeastern Mexico. During 2016, samples of landraces of yellow maize were collected and integrated into 32 populations and experimental varieties, which were planted in two locations in Oaxaca, Mexico, under a random block design. At harvest, a sample of grain was taken, which was grounded to evaluate the polyphenolic compound contents and antioxidant activity by UV–visible spectrophotometry, and macro- and microelement contents were determined using inductively coupled plasma–optical emission spectrometry. The effect of crop location was significantly greater than the effects of populations and location-population interaction on polyphenol contents and concentration of Ca, P, Mg, K, Na, S, Cu, Fe, Mn and Zn. In the Amatengo locality, a higher macroelement contents were recorded, and in the second locality, the concentration of microelements, polyphenols, and flavonoids contents were higher. The populations showed high variability, with significant interactions with crop location in bioactive compounds, antioxidant activity and Ca, Cu, Na, Mn and S contents.