In recent years, the proportion of Dolichospermum (formerly known as Anabaena) has increased trends in Lake Taihu. In order to estimate the spatial differences and driving factors of long-term trends of Dolichospermum in Lake Taihu, we studied the long-term trends of Dolichospermum biomass in different areas of Lake Taihu in spring from 2005 to 2019, and investigated the effects of both spring and winter meteorological conditions (temperature, duration of sunshine, windspeed and rainfall) and nutrient levels (total nitrogen and total phosphorus). The monitoring data of Lake Taihu showed that spring Dolichospermum increased from 2005 to 2019, which mainly occurred in Zhushan Lake, followed by the Lake Center, Meiliang Bay, South Lake. The analysis of partial least squares path modeling (PLS-PM) showed that the main driving factors of the changes in the biomass of Dolichospermum in different areas were different. In the Lake Center, the biomass of Dolichospermum in spring was mainly affected by winter climatic conditions (temperature, windspeed and sunshine), and secondly by spring nutrients and spring climatic conditions. In Meiliang Bay, Zhushan Lake, and South Lake, the biomass of Dolichospermum in spring was mainly affected by spring climatic conditions. In Meiliang Bay and Zhushan Lake, spring windspeed and sunshine duration were significant factors influenced the biomass of Dolichospermum in spring. In South Lake, the main driving factors for the biomass of Dolichospermum in spring were the sunshine and the temperature in spring. This study conducted the temporal and spatial distribution characteristics and influencing factors of nitrogen-fixing cyanobacteria in Lake Taihu from a long-term sequence perspective, and provided a theoretical basis for the prevention and control of algal blooms and eutrophication in different areas of Lake Taihu.