Magnesium (Mg) and its alloys hold great potential as an energy-saving structural material for automative, aerospace applications. However, the use of Mg alloys has been limited due to poor ductility and formability. Poor mechanical properties of Mg alloys origin from the insufficient number of slip systems, and deformation twinning plays an important role to accommodate plastic deformation. Here, we report a comprehensive experimental and modeling study to understand crystal size effect on the transformation in deformation modes in twin oriented Mg single crystals. The experiments reveal two regimes of size effects: (1) single twin propagation, where a typical "smaller the stronger" behavior was dominant in pillars ≤ 18 µm in diameter, and (2) twin-twin interaction, which results in anomalous strain hardening in pillars > 18 µm. Molecular dynamics simulations further indicate a transition from twinning to dislocation mediated plasticity for crystal sizes below a few hundred nanometers. Our results provide new understanding of the fundamental deformation modes of twin oriented Mg from nano-scale to bulk, and insights to design Mg alloys with superior mechanical properties through dimensional refinement. This subsequently can materialize into more utilization of Mg alloys as a structural material in technologically relevant applications.