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Introduction We investigated the longitudinal relationship between cortical amyloid deposition, anxiety, and depression and the risk of incident mild cognitive impairment (MCI). Methods We followed 1440 community-dwelling, cognitively unimpaired individuals aged ≥ 50 years for a median of 5.5 years. Clinical anxiety and depression were assessed using Beck Anxiety and Depression Inventories (BAI, BDI-II). Cortical amyloid beta (Aβ) was measured by Pittsburgh compound B positron emission tomography (PiB-PET) and elevated deposition (PiB+) was defined as standardized uptake value ratio ≥ 1.48. We calculated Cox proportional hazards models with age as the time scale, adjusted for sex, education, and medical comorbidity. Results Cortical Aβ deposition (PiB+) independent of anxiety (BAI ≥ 10) or depression (BDI-II ≥ 13) increased the risk of MCI. There was a significant additive interaction between PiB+ and anxiety (joint effect hazard ratio 6.77; 95% confidence interval 3.58–12.79; P = .031) that is, being PiB+ and having anxiety further amplified the risk of MCI. Discussion Anxiety modified the association between PiB+ and incident MCI.