Zambia conducted a measles and rubella (MR) vaccination campaign targeting children 9 months to younger than 15 years of age in 2016. This campaign was the first introduction of a rubella-containing vaccine in Zambia. To evaluate the impact of the campaign, we compared the MR seroprevalence estimates from serosurveys conducted before and after the campaign in Southern Province, Zambia. The measles seroprevalence increased from 77.8% (95% confidence interval [CI], 73.2-81.9) to 96.4% (95% CI, 91.7-98.5) among children younger than 15 years. The rubella seroprevalence increased from 51.3% (95% CI, 45.6-57.0) to 98.3% (95% CI, 95.5-99.4). After the campaign, slightly lower seroprevalence remained for young adults 15 to 19 years old, who were not included in the campaign because of their age. These serosurveys highlighted the significant impact of the vaccination campaign and identified immunity gaps for those beyond the targeted vaccination age. Continued monitoring of population immunity can signal the need for future targeted vaccination strategies.