The design of microchannel based heat sinks for advanced electronic component continues to receive research interest, especially with the ever-increasing density of advanced chips with concomitant increase in heat generation. One aspect of microchannel heat sink design objectives is the optimum employment of non-uniform heat dissipation through the channel length. Two dominant schools in the performance optimization of non-uniform heat sinks are: 1) entropy minimization and 2) thermal resistance minimization. These two approaches usually result in contradictory conclusions: one recommending the use of increasing heat flux, the other recommending a decreasing heat flux. The current study seeks to explain this discrepancy by experimentally and numerically studying the heat transfer mechanisms in a single microchannel tube under the effect of non-uniform heat flux. This study presents an experimental framework capable of generating a wide range of pre-specified heat flux profiles over a single microchannel, mimicking actual heat flux profiles observed in thermo-electronic devices. We employ three flux profiles: 1) hotspots located at different locations with uniform background heat flux, 2) linearly ascending heat flux, and 3) linearly descending heat flux. The results show good agreement between numerical simulations and experimental measurements and provide insights into the microchannel tube's fundamental heat transfer mechanisms. Based on these insights, the study provides design guidelines to enhance microchannel heat sink performance under non-uniform axial heat fluxes. Finally, the discrepancy between entropy and heat resistance minimization approaches is explained.