Pyrethroid resistance is a major concern for malaria vector control programs that predominantly rely on insecticide-treated mosquito nets (ITNs). Contradictory results of the impact of resistance have been observed during field studies. We combined continent-wide estimates of pyrethroid resistance in Anopheles gambiae from 2006 to 2017, with continent-wide survey data to assess the effect of increasing pyrethroid resistance on the effectiveness of ITNs to prevent malaria infections in sub-Saharan Africa. We used a pooled-data approach and a meta-regression of survey regions to assess how pyrethroid resistance affects the association between ITN ownership and malaria outcomes for children 6 to 59 months of age. ITN ownership reduced the risk of malaria outcomes according to both the pooled and meta-regression approaches. According to the pooled analysis, there was no observed interaction between ITN ownership and estimated level of pyrethroid resistance (likelihood ratio [LR] test, 1.127 for malaria infection confirmed by the rapid diagnostic test, P = 0.2885; LR test = 0.161 for microscopy-confirmed malaria infection, P = 0.161; LR test = 0.646 for moderate or severe anemia, P = 0.4215). Using the meta-regression approach to determine the level of pyrethroid resistance did not explain any of the variance in subnational estimates of ITN effectiveness for any of the outcomes. ITNs decreased the risk of malaria independent of the levels of pyrethroid resistance in malaria vector populations.