There are alternative methods for estimation of phytoplankton primary production (PP) that are fundamentally different in the calculation approach. The process-oriented PP model is a mechanistic, empirically derived method based on the photosynthesis–light relationships. The population dynamics-based PP calculation, which is a synthetic method, provides a production estimate based on population dynamics of phytoplankton. These alternative methods were here compared with regard to production estimates and linked to enhance the performance of the existing models of population dynamics applied to a wide variety of lakes worldwide in terms of morphometry, nutrient status, and light environments. Estimates of primary production were shown to be sensitive to changes in phytoplankton sinking and zooplankton grazing rates in both methods. Production estimates in the process-oriented PP model were also sensitive to light-associated parameters such as day length. Although the production estimated from the population dynamics-based PP calculation tended to be lower than that from the process-oriented PP model irrespective of lake morphometry, production estimates calculated from both methods with standard parameterization were comparable when production was estimated on an annual timescale. However, it was also shown that the alternative methods could produce different production estimates when estimated on shorter timescales such as cyanobacterial blooms in summer. Cyanobacteria with low mortality due to grazing and sinking losses have been considered as trophic bottlenecks, but there is increasing evidence that their mortality is, to a considerable extent, due to parasitic pathogens. In the case of cyanobacterial blooms, an addition of parasite-related loss term (19–33% of standing stock) resulted in a resolution of the difference in production estimates between the methods. These analyses theoretically support the critical role of parasitism and resolve the bottleneck problem in aquatic ecosystem metabolism.