This study sought to assess the effect of job security on the commitment of teachers in the Cape Coast Metropolis of Ghana. The study further assessed the mediating role of career satisfaction in the relationship between job security and organizational commitment. Using an explanatory survey design, 228 senior high school teachers were systematically selected and surveyed accordingly. The estimated target population was 530 teachers. An internal consistency of .807 was recorded for the instrument. Data processing and analysis were done using SPSS and SMART PLS to assess the effect of job security on the four dimensions of organizational commitment (affective, continuance, normative, and value commitment). The measurement model met all the quality criteria. It was found that job security had a positive influence on all four dimensions of organizational commitment as well as career satisfaction. Similarly, career satisfaction had a positive influence on all four dimensions of organizational commitment. Furthermore, career satisfaction mediated the relationships among job security and all dimensions of organizational commitment except value commitment. Thus, the findings suggest that Ghana Education Service should institute policies and measures that enable teachers to feel more secure in their job, and increase their opportunities for career development in Ghana’s public senior high schools. Additionally, teachers should take advantage of human resource development policies initiated by their respective institutions to increase the level of their career satisfaction and consequently, their commitment to their respective schools.