Children's blood lead concentrations have been closely monitored over the last two decades in the United States. The bio-monitoring surveillance data collected in local agencies reflected the local temporal trends of children's blood lead levels (BLLs). However, the analysis and modeling of the long-term time series of BLLs have rarely been reported. We attempted to quantify the long-term trends of children's BLLs in the city of Syracuse, New York and evaluate the impacts of local lead poisoning prevention programs and Lead Hazard Control Program on reducing the children's BLLs. We applied interrupted time series analysis on the monthly time series of BLLs surveillance data and used ARMA (autoregressive and moving average) models to measure the average children's blood lead level shift and detect the seasonal pattern change. Our results showed that there were three intervention stages over the past 20 years to reduce children's BLLs in the city of Syracuse, NY. The average of children's BLLs was significantly decreased after the interventions, declining from 8.77μg/dL to 3.94μg/dL during1992 to 2011. The seasonal variation diminished over the past decade, but more short term influences were in the variation. The lead hazard control treatment intervention proved effective in reducing the children's blood lead levels in Syracuse, NY. Also, the reduction of the seasonal variation of children's BLLs reflected the impacts of the local lead-based paint mitigation program. The replacement of window and door was the major cost of lead house abatement. However, soil lead was not considered a major source of lead hazard in our analysis.