The study reports on immunization coverage trends in SA for the period 2001–2010 at the province and district levels. The data included routine immunization for 1st and 2nd doses of measles vaccine (MCV1, MCV2), SIAs, 1st dose of Bacille Calmette-Guérin vaccine, 1st and 3rd doses of oral polio vaccine (OPV1, OPV3), 3rd dose of Diphtheria–Tetanus–Pertussis–Haemophilus-influenzae-B vaccine (DTP-Hib3), and the number of under-one-year-olds having completed a primary course of immunization (Imm1). A regression model looked at the SIA impact on routine coverage. It concludes that the heterogeneity in measles vaccination coverage across SA districts challenges the goal of measles elimination in SA and SSA. The reduction in routine immunization coverage associated with the occurrence of SIAs (Supplemental immunization activity) raises the legitimate concern that SIAs may negatively impact health systems’ functioning.