This study systematically reviews the evidence of the association between life course social mobility and tooth loss among middle-aged and older people. PubMed, Scopus, Embase, and Web of Science were systematically searched in addition to gray literature and contact with the authors. Data on tooth loss were collated for a 4-category social mobility variable (persistently high, upward or downward mobility, and persistently low) for studies with data on socioeconomic status (SES) before age 12 y and after age 30 y. Several study characteristics were extracted to investigate heterogeneity in a random effect meta-analysis. A total of 1,384 studies were identified and assessed for eligibility by reading titles and abstracts; 21 original articles were included, of which 18 provided sufficient data for a meta-analysis with 40 analytical data sets from 26 countries. In comparison with individuals with persistently high social mobility, the pooled odds ratios (ORs) for the other categories were as follows: upwardly mobile, OR = 1.73 (95% CI, 1.53 to 1.95); downwardly mobile, OR = 2.52 (95% CI, 2.19 to 2.90); and persistently low, OR = 3.96 (95% CI, 3.13 to 5.03). A high degree of heterogeneity was found(I² > 78%), and subgroup analysis was performed with 17 study-level characteristics; however, none could explain heterogeneity consistently in these 3 social mobility categories. SES in childhood and adulthood is associated with tooth loss, but the high degree of heterogeneity prevented us from forming a robust conclusion on whether upwardly or downwardly mobile SES may be more detrimental. The large variability in effect size among the studies suggests that contextual factors may play an important role in explaining the difference in the effects of low SES in different life stages (PROSPERO CRD42018092427).