Atypical disease presentations are common in older adults with COVID-19. The objective of this study was to determine the prevalence of atypical and typical symptoms in older adults with COVID-19 through progressive pandemic waves and the association of these symptoms with in-hospital mortality. This retrospective cohort study included consecutive adults aged over 65 years with confirmed COVID-19 infection who were admitted to seven hospitals in Toronto, Canada, from 1 March 2020 to 30 June 2021. The median age for the 1786 patients was 78.0 years and 847 (47.5%) were female. Atypical symptoms (as defined by geriatric syndromes) occurred in 1187 patients (66.5%), but rarely occurred in the absence of other symptoms (n = 106; 6.2%). The most common atypical symptoms were anorexia (n = 598; 33.5%), weakness (n = 519; 23.9%), and delirium (n = 449; 25.1%). Dyspnea (adjusted odds ratio [aOR] 2.05; 95% confidence interval [CI] 1.62–2.62), tachycardia (aOR 1.87; 95% CI 1.14–3.04), and delirium (aOR 1.52; 95% CI 1.18–1.96) were independently associated with in-hospital mortality. In a cohort of older adults hospitalized with COVID-19 infection, atypical presentations frequently overlapped with typical symptoms. Further research should be directed at understanding the cause and clinical significance of atypical presentations in older adults.