BackgroundMalaria control interventions, including insecticide-treated nets (ITNs), were scaled up nationwide in Malawi during 2000–10. We assessed trends and associations of ITN coverage, malaria morbidity, and all-cause mortality in children under 5 years of age under programmatic conditions in Malawi during 2000–10. MethodsTrends in household ITN ownership, malaria parasitaemia, and anaemia (haemoglobin <80 g/L) prevalence, and all-cause under-5 mortality per 1000 livebirths (ACCM) were assessed from national population-based household surveys conducted during 2000–10. Random-effects logistic regression models assessed the association between household ITN ownership and malaria parasitaemia, or anaemia prevalence in children 6–30 months of age using subnational anaemia and parasitaemia survey data. We employed a random-effects Poisson regression model to assess the association between district ITN distributions and child malaria cases using integrated disease surveillance and response (IDSR) facility data. At the district level, we used a Poisson regression model to assess the association between household ITN ownership and child mortality using data from the 2010 Malawi Demographic and Health Survey. FindingsHousehold ITN ownership increased from 27·4% (95% CI 25·9–29·0) in 2004, to 56·8% (55·6–58·1) in 2010. Malaria parasitaemia decreased from 60·5% (95% CI 53·0–68·0) in 2001, to 20·4% (15·7–25·1) in 2009, in children aged 6–35 months. Anaemia decreased from 20·4% (95% CI 17·3–24·0) in 2004, to 13·1% (11·0–15·4) in 2010, in children aged 6–23 months. ACCM decreased by 41% from 188·3 deaths per 1000 livebirths (95% CI 179·2–197·3) during 1996–2000, to 112·1 per 1000 livebirths (106·1–118·0) during 2006–10. Household ITN ownership was protective against malaria parasitaemia (odds ratio 0·81, 95% CI 0·72–0·92) and anaemia (0·77, 0·70–0·86) after controlling for other covariates. ITN distributions per 1000 population were not significantly associated with malaria cases at IDSR facilities. District-level household ITN ownership was significantly associated with child survival (incidence rate ratio 0·55, 95% CI 0·31–0·99) after controlling for other covariates. InterpretationHousehold ITN ownership was protective against malaria parasitaemia, anaemia, and child mortality. Scale-up of malaria control interventions during 2000–10 was likely associated with improved child survival in Malawi. FundingFinancial support for this study was received from the United States President's Malaria Initiative.