Emphasis on lean premixed combustion in modern low NOX combustion chambers limits the air available for cooling the combustion liner. Hence, the development of optimized liner cooling designs is imperative for effective usage of available coolant. An effective way to cool a gas turbine combustor liner is through effusion cooling. Effusion cooling (also known as full-coverage film cooling) involves uniformly spaced holes distributed throughout the liner’s curved surface area. This study presents findings from an experimental study on the characterization of the overall cooling effectiveness of an effusion-cooled liner wall, which was representative of a can combustor under heated flow (non-reacting) and lean-combustion (reacting) conditions. The model can combustor was equipped with an industrial swirler, which subjected the liner walls to engine representative flow and combustion conditions. In this study, two different effusion cooling liners with an inline and staggered arrangement of effusion holes have been studied. Non-dimensionalized streamwise hole-to-hole spacing (z/d) and spanwise hole-to-hole spacing (r/d) of 10 were used for both the effusion liners. These configurations were tested for five different blowing ratios ranging from 0.7 to 4.0 under both reacting and non-reacting conditions. The experiments were carried out at a constant main flow Reynolds number (based on combustor diameter) of 12,500. The non-reacting experiments were carried out by heating the mainstream air, and the reacting experiments were carried out under flame conditions at a total equivalence ratio of 0.65. Infrared thermography (IRT) was used to measure the liner outer surface temperature, and detailed overall effectiveness values were determined under steady-state conditions. It was observed that overall cooling effectiveness trends were different under reacting and non-reacting conditions. The cooling effectiveness for the non-reacting experiments exhibited a decreasing trend, and no consistent location of minimum cooling effectiveness was observed for the range of blowing ratios investigated in this study. For the reacting cases, the cooling effectiveness first follows a decreasing trend, reaches a distinct minimum, and then increases till the end of the combustor. Under non-reacting conditions, the staggered configuration was 9–25% more effective than inline configuration, and under reacting conditions, the staggered configuration was 4–8% more effective than inline configuration. From this study, it is clear that the coolant flame interaction for the reacting experiments impacted the liner cooling effectiveness and led to different overall cooling effectiveness distribution on the liner when compared with the non-reacting experiments.