Background: Stress among prison inmates is a neglected psychological health issue, but this phenomenon seems worse in Ghana’s prisons. This study examined the stress levels, predictors and management strategies utilized among inmates at Ankaful Prison Complex. Method: This survey sampled 1160 inmates using the census approach at the Ankaful Prison Complex with a self-developed questionnaire for the data collection. Frequency counts, one-way ANOVA, and multiple regression analysis were applied to the data. Results: The findings indicate that more than half of the inmates were moderately or highly stressed. Specifically, inmates at the Maximum Security Prison were the most stressed, followed by Annex Prison, Communicable Disease Prison, and the least, Main Camp Prison inmates. Inmate engagement in exercises, sporting activities, visit and chat with colleagues, and family connectedness outside the prison were stress-management strategies. Inmates’ self-reported stress levels were influenced by the prison of custody and state of depression. Conclusion: The moderate to high stress levels identified among inmates of Ankaful Prison Complex are influenced by person–environment factors. Management of the Ankaful Prison Complex is encouraged to initiate health screening services for inmates on common mental health challenges such as stress and to promote functional stress reduction interventions to improve prisoners’ mental health and overall well-being.