Many aggregation‐induced emission (AIE) molecules based on tetraphenylethylene (TPE) structure have been synthesized, but a clear understanding of the photophysical difference between different isomeric pyridyl‐based tetraphenylethylene molecules remains elusive. Herein, we designed a series of isomeric tetraphenylethylene‐pyridines (o‐Py‐TPE, m‐Py‐TPE, p‐Py‐TPE) to investigate the influence of the position of N atoms in the pyridine subunit on the photophysical property of the whole molecule by detailed DFT calculations and single crystal structures analysis. All compounds show typical AIE properties, and notably, the meta pyridyl isomer (m‐Py‐TPE) shows the highest solid photoluminescence quantum yield (PLQY) up to 64.56%. Further investigation and DFT calculations indicate that the center C=C bond dihedral angles of the TPE subunit in the solid state of these compounds, which are affected by C−H···π interaction, play a vital role in their emission and PLQY properties. This work provides underlying principles for the design of pyridyl‐based TPE molecules with high photoluminescent performance in the future.