Despite high reported coverage for routine and supplementary immunization, in 2010 in Malawi, a large measles outbreak occurred that comprised 134,000 cases and 304 deaths. Although the highest attack rates were for young children (2.3%, 7.6%, and 4.5% for children <6, 6–8, and 9–11 months, respectively), persons >15 years of age were highly affected (1.0% and 0.4% for persons 15–19 and >19 years, respectively; 28% of all cases). A survey in 8 districts showed routine coverage of 95.0% for children 12–23 months; 57.9% for children 9–11 months; and 60.7% for children covered during the last supplementary immunization activities in 2008. Vaccine effectiveness was 83.9% for 1 dose and 90.5% for 2 doses. A continuous accumulation of susceptible persons during the past decade probably accounts for this outbreak. Countries en route to measles elimination, such as Malawi, should improve outbreak preparedness. Timeliness and the population chosen are crucial elements for reactive campaigns.