Nanotwinned Ni-Mo-W alloys possess a combination of unique mechanical and thermal properties, such as ultrahigh strength and microstructural stability, which are correlated with the presence of densely packed growth twins. In a previous study, the ultrahigh compressive strength of Ni84Mo11W5 (atomic percent) micropillars was associated with the formation of highly localized shear bands, but the trigger for such localized plasticity was not identified. Here, Ni86Mo3W11 (atomic percent) micropillars were carefully compressed to various levels to uncover the nanoscale deformation mechanisms that trigger the strain localization. Post-mortem transmission electron microscopy investigations of pillars after the first measurable strain burst revealed ∼50 nm thick shear bands consisting of reoriented and twin-free grains, while the columnar grains adjacent to the shear bands were partly detwinned. More importantly, unlike the Mo-rich pillars, the W-rich pillars showed discernible plasticity before the first strain burst. Close inspection made before the formation of a mature shear band revealed a detwinning region of ∼30 nm thickness that aligned more parallel to the coherent twin boundaries, and multiple nanotwins truncated with incoherent twin boundaries were resolved between the detwinning band and the nanotwinned grains. These observations strongly suggest detwinning, facilitated by migration of incoherent twin boundaries, to be the precursor to strain localization and the intensive shear banding observed in nanotwinned Ni-Mo-W alloys. Comparing the present results with the literature further highlights the general role of detwinning in governing the plastic behavior of nanotwinned alloys with a wide range of stacking fault energy.