Human activities and climate change are two major stressors affecting lake ecosystems as well as phytoplankton communities worldwide. However, how the temporal dynamics of phytoplankton are directly or indirectly linked to anthropogenic activities and climatic oscillation remains unclear. We assessed the annual trends (1988-2018) in phytoplankton abundance (PA) in Lake Dongting, China and related it to five groups of variables characterizing human activities, global climate oscillation, water nutrients, hydrology, and meteorology. We found a significant increase in PA, urbanization (Upop), total nitrogen (TN), fertilizer application (FA), number of summer days (SU), and the warm speed duration index (WSDI) and a significant decrease in the water discharge of three inlets (TIWD) and the sediment discharge of three inlets (TISD) and four tributaries (FTSD) and the net sediment deposition (NSD). However, no significant annual trends were observed for the number of rainstorm days (R50mm), the simple precipitation intensity index (SDII) and yearly anomalies of El Nino-Southern oscillation events (ENSOi). Cross-correlation Function analyses demonstrated that the operation of the Three George Dam (TGD) strengthened the effects of hydrology, rainfall patterns and ENSOi on phytoplankton, but strongly weakened the association between water nutrients, human activities and phytoplankton abundance. Path analysis revealed that TP, TN, FA, R50 mm as well as WSDI had a direct positive effect on PA, while a direct negative effect was found for ENSOi, NSD and TISD. Human activities (Upop and FA), warming (WSDI and SU), and rainfall patterns (SDII and R50 mm) exerted indirect controls on phytoplankton through changes in water nutrients and hydrology. Climate change (ENSOi) had a direct effect on PA, but also showed twelve indirect pathways via changes in hydrology and meteorology (both positive and negative effects were found). Overall, meteorology contributed most markedly to the variations of PA (29.3%), followed by hydrology (25.3%), human activities (24%), water nutrients (10.5%), and ENSOi (1.9%). Our results highlight a strongly causal connection between human activities as well as global climate change and phytoplankton and the benefits of considering multiple environmental drivers in determining the temporal dynamics of lake biotic communities.