This study reveals a local strain‐dependent etching behavior that enables the formation of distinguished etching patterns in differently strained chemical vapor deposited (CVD) 2D molybdenum disulfide (MoS2) monolayers. It is demonstrated that when the local tensile strain of CVD 2D MoS2 is as uniformly low as ɛ ≈ 0.33% or less, the oxidative etching pattern possesses conventional triangular etching pits (TEPs), while when the local tensile strain is as uniformly high as ɛ ≈ 0.55% or larger, the oxidative etching pattern consist of uniformly oriented hexagonal etching channels (HECs). More interestingly, when the CVD 2D MoS2 monolayer has heterogenous strain distribution from ɛ ≈ 0.55% (center region) to ɛ ≈ 0.33% (perimeter region), the oxidative etching pattern comprise of non‐uniformly hexagonal‐mixed‐parallel etching channels (HPECs). The further characterization and analysis reveal the formation mechanism of such strain‐dependent etching patterns is built on the local strain‐related fractures propagation under oxidative etching, as well as the anisotropy fractures‐based oxidative etching kinetics. This study may enhance the understanding of the relationship between etching and growth features of 2D TMDs, and paves the way to etching‐nanostructured (or defect) engineering of 2D TMDs and other 2D materials for potential applications in electrocatalysis and optoelectronics.