ABSTRACT Background Emerging evidence indicates that the apolipoprotein E (APOE) ε4 exacerbates α‐synuclein pathology. Objective To determine whether APOE ε4 contributes to motor progression in early Parkinson's disease (PD). Methods Longitudinal data were obtained from 384 patients with PD divided into APOE ε4 carriers (n = 85) and noncarriers (n = 299) in the Parkinson's Progression Marker Initiative. Participants underwent yearly motor assessments over a mean follow‐up period of 78.9 months. Repeated measures and linear mixed models were used to test the effects of APOE ε4. Results The motor progression was significantly more rapid in patients with PD carrying APOE ε4 than in noncarriers (β = 0.283, P = 0.026, 95% confidence interval: 0.033–0.532). Through subgroup analysis, we found that the effect of APOE ε4 was significant only in patients with high amyloid β burden (β = 0.761, P < 0.001, 95% confidence interval: 0.0356–1.167). Conclusions APOE ε4 may be associated with rapid motor progression in PD. © 2021 International Parkinson and Movement Disorder Society