The study sought to investigate the key factors that influence inflation dynamics in Ghana. The study found that inflation in Ghana is determined primarily by inflation persistence, reflecting price expectations, domestic food prices, petroleum prices and exchange rate. The other determinants of inflation used in this study such as money supply and world food prices weakly affect domestic inflation. The study also recommended that anchoring inflation expectations and managing exchange rate misalignment remains key policy strategies in any effort and attempt by the monetary authorities to achieving and maintaining price stability in the country coupled with moderating the negative effects of other inflation determining factors.