Strain weakening plays an important role in the continent-scale flow of rocks and minerals, including ice. In laboratory experiments, strain weakening coincides with microstructural changes including grain size reduction and the development of crystallographic preferred orientation (CPO). To interrogate the relative contributions of CPO development and grain size towards the strain weakening of viscously anisotropic minerals at very high homologous temperatures (Th ≥ 0.9), we deformed initially isotropic polycrystalline ice samples to progressively higher strains. We subsequently combined microstructural measurements from these samples with ice flow laws to separately model the mechanical response arising from CPO development and grain size reduction. We then compare the magnitudes of strain weakening measured in laboratory experiments with the magnitudes of strain weakening predicted by the constitutive flow laws. Strain weakening manifests as strain rate enhancement after minimum strain rate under constant load conditions, and as a stress drop after peak stress under constant displacement rate conditions. However, flow laws that only consider grain size evolution predict a nominally constant sample strength with increasing strain. On the other hand, flow law modelling that solely considers CPO effects can accurately reproduce the experimental strain weakening measurements. These observations suggest that at high homologous temperatures (Th ≥ 0.9), CPO development governs the strain weakening behaviour of viscously anisotropic materials like ice. Grain size, on the other hand, plays a negligible role in strain weakening under such conditions. Overall, we suggest that geodynamic and glaciological models should incorporate evolving CPOs to account for strain weakening, especially at high homologous temperatures.