Prion diseases, also known as transmissible spongiform encephalopathies, are a rare form of neurodegenerative diseases in which the misfolding of the healthy cellular prion protein (PrPC) into the diseased PrPSc form spreads throughout the structures of the central nervous system (CNS). The most common variant of prion diseases is sporadic Creutzfeldt-Jakob disease (sCJD), but diagnosis is challenging due to long incubation times and similarities with other neurodegenerative diseases. The biomarker total tau (t-tau) from cerebrospinal fluid plays an important role due to its increased concentration caused by neurodegeneration in diagnosing and classifying prion diseases. The aim of this meta-analysis was to analyze the contribution of t-tau towards diagnosis, classification and prognosis of prion strains in prion diseases by employing meta-analytical methods in RStudio. The heterogeneity and publication bias of the sensitivity and specificity of t-tau were statistically evaluated across 18 studies selected based on a systematic literature search, as well as within subgroups of the type of control group (healthy, non-CJD, Alzheimer’s Disease). The results showed that t-tau has a mean sensitivity of 83.5% and mean specificity of 86.1%; the subgroups range around similar values with t-tau performing best in the non-CJD subgroup. Heterogeneity analysis demonstrated moderate to high heterogeneity across the studies and funnel plots indicated a small publication bias. In conclusion, t-tau showed high sensitivity and specificity in differentiating sCJD from other neurodegenerative diseases, but an increased accuracy can be achieved by combining biomarkers. Further research addressing the classification and prognosis of prion strains with t-tau is needed.