Anaerobic digestion (AD) is an established process for integrating waste management with renewable energy and nutrient recovery. Much of the research in this field focuses on the utilisation of new substrates, yet their effects on operational aspects such as fluid behaviour and power requirement for mixing are commonly overlooked, despite their importance for process optimisation. This study analysed rheological characteristics of samples from 21 laboratory-scale continuous stirred-tank biogas reactors (CSTBRs) digesting a range of substrates, in order to evaluate substrate effect on mixing efficiency and power demand through computational fluid dynamics (CFD). The results show that substrate and process parameters, such as solids content and organic loading, all have a significant effect on CSTBR fluid rheology. The correlation levels between rheological and process parameters were different across substrates, while no specific fluid behaviour patterns could be associated with substrate choice. Substrate should thus be considered an equally important rheology effector as process parameters. Additional substrate-related parameters should be identified to explain the differences in correlations between rheological and process parameters across substrate groups. The CFD modelling revealed that the rheology differences among the AD processes have significant implications for mixing efficiency and power demand of the CSTBRs, highlighting the importance of considering the substrate-induced effects on CSTBR rheology before including a new substrate.