Both motoric cognitive risk (MCR) syndrome and C-reactive protein (CRP) serum levels have been separately associated with increased risk of incident major neurocognitive disorder. The study aims to compare the CRP serum levels of older adults with and without MCR and to examine the associations of MCR and CRP serum levels and their combination with incident major neurocognitive disorder. 915 individuals participating in an older adult's population-based observational cohort study with a 3-year follow-up design were selected. MCR and CRP serum levels were collected at baseline. Incident major neurocognitive disorder was measured at annual follow-up visits using the Modified Mini-Mental State Examination (≤79/100) and simplified instrumental activity daily living scale (<4/4) score values. The prevalence of MCR at baseline assessment was 3.7%. The overall incidence of major neurocognitive disorder was 3.0%. MCR alone (hazard ratio = 25.36 with 95% confidence interval = [6.25-102.95] and p ≤ .001) and MCR with a high CRP serum level (hazard ratio = 5.61, with 95% confidence interval [1.29-24.26] and p = .021) were significantly associated with incident major neurocognitive disorder. MCR is a significant risk factor for predicting major neurocognitive disorder in older adults, while serum CRP levels are not. In addition, serum CRP levels reduce the predictive strength of MCR for major neurocognitive disorder.