<p>Thermoelectric materials are of great interest for heat energy harvesting applications. One such promising material is TlGaSe₂, a 2D-layered, <i>p</i>-type semiconducting ternary chalcogenide. Recent reports show it can be processed as a thin film, opening the door for large-scale commercialization. However, TlGaSe₂ is prone to stacking faults along the [001] stacking direction and their role in its thermoelectric properties has not yet been understood. Herein, TlGaSe₂ is investigated via (scanning) transmission electron microscopy and first-principles calculations. Stacking faults are found to be present throughout the material, as density functional theory calculations reveal a low stacking fault energy of ~12 mJ m⁻². Electron transport calculations show an enhancement of thermoelectric power factors when stacking faults are present. This implies the presence of stacking faults is key to the material’s excellent thermoelectric properties along the [001] stacking direction, which can be further enhanced by doping the material to carrier concentrations of ~10¹⁹cm⁻³.</p>