Algeria is the largest country of Africa, with a population of 40 million inhabitants living in disparate environments from the Sahara to the large cities of the Mediterranean coast. The molecular epidemiology of hepatitis B virus (HBV) variants has been partially described, but variations in the seroprevalence of HBV surface antigen (HBsAg) throughout the Algerian territories are still poorly described. We analyzed demographic features of new cases of chronic infection collected in 41 administrative regions (covering 92% of the population) in 2013. The mean age of the 1876 HBsAg(+) patients was 36.8 ± 14.2 years, with a slight excess of males (54%). The seroprevalence of HBV early antigen (HBeAg) was 9.3%, and the mean virus load was 3.2 ± 1.8 log IU/ml. A subset of 15.2% of patients was already cirrhotic at disease discovery. An important heterogeneity was observed throughout the country, with nine regions displaying a significant excess of cases. These regions formed four distinct foci located in distant parts of the country: Adrar-Bechar (southwest), El-Oued-Tebessa (east), M'Sila-Sétif (north central) and Oran-Aïn Temouchent (northwest). An excess of cases was found as well in the national capital Algiers. Patients from southern regions with an excess of cases (Bechar, Adrar, El Oued) were significantly younger (32.0 ± 10.7 years), as were patients from the regions of Bejaia and Bouira (32.1 ± 10.6). The southwestern regions were also marked by a significant imbalance of the sex ratio (58 vs 39% of female cases, P = 4.5 E-5). The highest HBeAg seroprevalence was observed in Setif (26.4 vs. 7.6%, OR = 4.3, 95% CI 2.6-6.5, P = 1.1 × 10-11) in accordance with the higher virus loads observed in the patients (3.9 ± 2.3 vs. 3.1 ± 1.6, P = 0.0002). In conclusion, we observed heterogeneity in HBsAg seroprevalence, demographic traits, and disease evolution in Algeria. Further studies are now warranted to shed light on these differences, which are presumably due to variability in transmission routes or in the infectivity of viral isolates.