The impact of weather variables on Culex pipiens L. (Diptera: Culicidae) population dynamics in the Po Valley, Northern Italy, a densely populated region containing the largest industrial and agricultural areas in Italy, was investigated. Monitoring of mosquitoes was carried out by using CO₂-baited traps without light, collecting data weekly from 1700 to 0900 hours during the period May–September, from 1997 to 2011. Daily minimum, average, and maximum relative humidity; daily minimum, maximum, and average temperature; rainfall; and hydroclimatic balance (rainfall-potential evapotranspiration) were obtained from three weather stations within the surveillance zone. The average population dynamic trend over the 15-yr period showed a bell-shaped curve with a major peak in June and a secondary peak at the end of August in the rural areas, whereas bimodality was not evidenced in the urban areas. The correlation analyses showed that the mosquito seasonal population and the population in the period of maximum West Nile virus circulation (August–September) was mostly affected by the relative humidity registered from March to July, particularly in May, and, to a lower extent, also by hydroclimatic balance registered in April–July, and by the rainfall occurred in June–July. In addition, the rate of increase of the population during the spring months influenced the development of the mosquito population of the following months.