Objectives Empirical evidence increasingly highlights the importance of general self-efficacy (GEF) in preventing disease and promoting quality of life. While it is already known that GEF varies with socio-demographic factors, health variables and personality traits, little is known about the influence of socio-political context. The objective of the study was to examine and compare GEF between 2014 and 2022 in East and West Germany and to test differences regarding sex. Study design In 2014 (N = 2506) and 2022 (N = 2508), two large representative cohorts from the German general population were surveyed about their GEF using the General Self-Efficacy Short Scale (ASKU). Methods A three-way ANCOVA were calculated to test the effect of region of residence, survey date, and sex controlling for age on GEF in a combined sample (N = 5014). Results There was a significant decrease in GEF between 2014 and 2022. Women reported lower GEF than men. A statistically significant interaction was found between survey date and sex and between survey date, region of residence and sex on GEF. Almost the same patterns were observed for the ability to solve difficult and complex tasks well, with the exception, that men in East Germany reported an increase in the ability to solve difficult and complex tasks well from 2014 to 2022. The ability to solve most problems independently and to solve challenging and complex tasks well was mainly influenced by education and household income, rather than by the date of the survey, the region of residence or sex. Conclusion Although regional differences in GEF were minimal, more pronounced variations emerged across sex and socioeconomic groups. These patterns likely stem from historical socio-political legacies and structural inequalities, potentially amplified by the impact of COVID-19 restrictions.