ABSTRACT Nigeria has the highest burden of measles worldwide, as measles vaccine uptake remains low. Recently, the second dose of the measles-containing vaccine (MCV2) was introduced as part of the routine immunization (RI) program, and this study examined how it changed the uptake of the measles vaccine and the factors associated with vaccination behavior. The Nigeria Multiple Indicator Cluster Survey (MICS) 2021 was used to compare measles vaccination uptake as well as factors associated with vaccination uptake between children before MCV2 introduction (cohort 1) and after the introduction (cohort 2). The overall rate of measles vaccine uptake was higher among cohort 1 (64%–95%) than among cohort 2 (56%–92%) in all zones because of younger age among cohort 2. The dropout from the first to second measles vaccines was similar between the cohorts (around 24%). Higher maternal education levels and higher household wealth levels were both correlated with the vaccine uptake or both cohorts but a positive correlation between the dropout and mother’s education level was observed only among cohort 2, especially in the North West and South West zones. The positive correlation between the dropout and mother’s education level among cohort 2 indicates that the introduction of MCV2 as part of RI might have helped to narrow the disparity in measles vaccine uptake in North West and South West zones. Further study is required to investigate strategies employed to reduce the disparity in these zones to apply nationwide.