Background/Objectives: Studies investigating the associations between life-course socioeconomic status (SES) and biological aging (the difference between biological and chronological age, Δage) have mostly been focused on epigenetic clocks and on a limited number of mediators. The aim of this study was to investigate this relationship using a blood-based aging clock, as well as the potential mediation of different factors including lifestyles or their proxies and physical and mental wellbeing. Methods: A deep-learning aging clock based on 36 blood markers was deployed, in a large Italian population cohort: the Moli-sani study (N = 4772; ≥35 years; 48% men). SES was defined as an eight-level trajectory over the life course, which was tested with Δage in linear models incrementally adjusted for age, sex, and prevalent health conditions. Moreover, the proportion of associations explained by diverse potential mediators, including diet, smoking, physical activity, alcohol, body mass index (BMI), and physical and mental quality of life (QoL) was estimated. Results: Compared to participants with a stably high SES, those showing an educational and financial downward trajectory were older than their CA (β (95%CI) = 1.28 (0.73–1.83) years), as were those with a stably low SES (0.75 (0.25–01.25) years). These associations were largely explained by the tested mediators (overall proportion: 36.2% and 66.3%, respectively), prominently by physical QoL (20.7% and 41.0%), BMI (16.8% and 34.3%), lifestyle (10.6% and 24.6%), and dietary inflammatory score (5.3% and 9.2%). Conclusions: These findings indicate that life-course socioeconomic inequalities are associated with accelerated biological aging, suggesting physical wellbeing and pro-inflammatory lifestyles as potential public health targets to slow down this process in susceptible socioeconomic strata of the population.