Cognitive-behavioral coping among teachers is an important issue of investigation due to the reported high prevalence of anxiety associated with the COVID-19 pandemic. Whereas several studies have assessed COVID-19 awareness of individuals as a predictor of anxiety, the moderating role of awareness in anxiety and coping mechanisms remains unclear. The study primarily examined the nexus between awareness of COVID-19 and (a) anxiety and (b) coping strategies, including the interaction effect of COVID-19-related awareness in the link between anxiety and coping strategies among senior high school teachers. A descriptive cross-sectional survey design was adopted to conveniently select 184 teachers from senior high schools in the Cape Coast Metropolis. Questionnaires were administered to the participants and data were analyzed with means, standard deviation, Pearson correlation, and linear regression statistical procedures. Summarily, the results revealed a negative relationship between COVID-19 awareness and anxiety levels of teachers. COVID-19-related anxiety significantly predicted coping mechanisms of teachers. Further, COVID-19 awareness significantly moderated the relationship between anxiety and coping strategies adopted. These findings imply that the public health education and mass awareness campaign programs on COVID-19 could act as buffers against the spread of COVID-19, its associated comorbidities, and help improve the mental health of teachers. Promoting adaptation to COVID-19 through the use of functional management strategies such as active coping and emotional support should be encouraged in the Cape Coast Metropolis among teachers.