Cyanobacterial blooms (CBs) in eutrophic lakes can cause various harmful issues to both humans and animals, disturb drinking water supply, and devastate lake ecosystems. Although great progresses have been made in many lakes from China and abroad on CBs prevention, mitigation and control, systematic research on the influencing factors of CBs in hypereutrophic plateau Lake Dianchi over a long time span is so far unavailable. This study comprehensively generalized both meteorological and water quality changes in Lake Dianchi during 1990–2015 on both yearly and monthly basis, separated Caohai from Waihai of Lake Dianchi regarding water quality variations, and investigated the individual and joint influencing meteorological and water quality factors on CBs using Spearman correlation, principal component analysis, and multivariate linear stepwise regression. Four specific lake regions, i.e. Caohai, northern Waihai, central Waihai, and southern Waihai, were respectively analyzed due to significant water quality heterogeneity. Results indicated that mild temperatures, low wind velocities, and hypereutrophic water conditions all favor CBs in Lake Dianchi, and the significant temperature rising trend may exacerbate severer CBs in the future. Despite configuration differences, the first principal components on CBs in the four sub-regions of Lake Dianchi were all consisted of meteorological factors, while water quality parameters especially total phosphorus concentrations contributed to the second principal component. Quantification of joint meteorological and water quality influencing factors on CBs needs further improvement, and largely relies on the accuracy of future weather forecasts, in order to set the goal of water quality improvement in each specific lake region for effective CBs management. Display omitted •Meteorological and water quality changes in Lake Dianchi (1990–2015) were analyzed.•The lake was divided into four sub-regions based on water quality heterogeneity.•In all regions, meteorological factors were the first principal component on CBs.•Meanwhile, water quality especially nutrients were the second principal component.•Accurate weather forecast helps to set the water quality standards across the lake.