Hepatitis B (HB) is a global public health burden which has impacted economies of many countries, particularly in sub-Saharan Africa. The effect is worse where there is lack of definite information regarding policy direction and capacity towards implementing interventions to control the transmission and spread of the infection. In this study, a SEIR deterministic compartmental model and a hybrid optimisation method for parameter estimation, similar to that of Awuah-Mensah et al. (2022), were used to analyse the regional distribution of HB in Ghana, a sub-Saharan African country. The regional epidemiological threshold parameters [Formula: see text] and herd immunity threshold parameters [Formula: see text] computed based on the estimated parameters for each of the regions ranged from a minimum of [Formula: see text] for Volta region in the southeast to a maximum of [Formula: see text] for Upper West region in the northwest of Ghana. These values of [Formula: see text] and [Formula: see text] indicated that HB persists in Ghana and the transmission and spread and the associated burden were found to generally increase from south to north of the country. Based on the estimated parameters, only Western region recorded a recovery rate of [Formula: see text]. The remaining nine regions recorded zero recovery rates. The trend of transmission and spread of the infection was also found to be positively related to poverty and health sector inequalities across the regions of the country.