The goal of our study was to explore the effect of living conditions on the odd of major and minor ECG abnormalities on a large region scale in Russia. For the analysis, cross-sectional data of the Russian study, ESSE-RF 2013–2014, were used. They were collected on a sample of 16,400 subjects from 10 regions of the Russia. ECG abnormalities were grouped into two categories: Major and Minor (sensu the 2009 version of the Minnesota Code Classification System). Regional living conditions were considered comprehensively via five indices combining 33 characteristics of the regions. The estimates were presented as odds ratios and their 95% confidence intervals. The prevalence values of major abnormalities in the sample were 8.4% among women and 9.4% among men (p = 0.021). The prevalence of minor abnormalities constituted 34.1% and 45.9%, respectively (p < 0.001). In men, the odd of major ECG abnormalities increased with the demographic depression growth (1.08: 1.04–1.12) and with industrial development growth in the region (1.12: 1.07–1.17). In women, an increase in the odd of major ECG abnormalities was directly associated with industrial development (1.12: 1.07–1.16) and inversely related to the economic development in the region (0.94: 0.89–0.99). The odd of minor ECG abnormalities in men and women declined with the growth of the regional economic development: OR of 0.95: 0.93–0.98, and OR of 0.92: 0.87–0.99, respectively. The study demonstrated an effect of regional living conditions of the Russian population on the odd of major and minor ECG abnormalities. The most stable and logically explainable relationships were obtained for industrial and economic characteristics of living conditions.