The inclusion of life satisfaction in government policies as a tracker of the social and economic progress of citizens has been recommended. This has encouraged the scientific investigation of life satisfaction levels of people in tandem with factors responsible for these levels. Only a few studies have attempted to do this in Ghana with mixed findings. This study, therefore, extends previous literature by examining the determinants of life satisfaction among Ghanaians in two ways: a full sample and a gender-stratified sample. We analysed cross-sectional data from the 2017/2018 Ghana Multiple Indicator Cluster Survey Six (MICS 6). A sample of 20,059 women and men of ages ranging from 15 to 49 years participated in this study. The Cantril’s Self-Anchoring Ladder Life Satisfaction scale was used to capture the life satisfaction of participants alongside relevant sociodemographic questions. About 35% of participants reported they were satisfied in life with males reporting more suffering levels [39.59%; 95% CI:36.38, 42.88] and females more thriving levels [36.41%; 95% CI:35.01, 37.84]. In the full sample multivariable model, gender, age, parity, education, marital status, wealth index, and region of residence were significantly associated with life satisfaction. Gender variations were also found across these associations. These findings collectively provide useful information for policymakers and practitioners to optimize interventions for the Ghanaian population aimed at improving life satisfaction. Evidence from this study also calls on the government of Ghana to begin tracking the life satisfaction of her citizens.