Decreasing form factors and diminishing numbers of thermal interfaces and spreading layers in modern, compact electronic packages result in non-uniform heat generation profiles at the chip level being transmitted directly to the heat sinks. An improved understanding of the effects of non-uniform heating on the heat dissipation limits in microchannel heat sinks has become essential. An experimental investigation is conducted to measure the location and magnitude of critical heat flux (CHF) in a microchannel heat sink exposed to a range of non-uniform heating profiles. A 12.7 mm X 12.7 mm silicon microchannel heat sink with an embedded 5 X 5 array of individually controllable heaters is used in the experiments. The microchannels in the heat sink are 240 mm wide and 370 μm deep, and are separated by 110 mm wide fins. The dielectric fluid HFE-7100 is used as the coolant, with an average mass flux in the heat sink of approximately 800 kg/m²s. High-speed visualizations of the flow are recorded to capture the CHF phenomena observed. A central ‘hotspot’ spanning the entire length of the heat sink in the flow direction (formed by heating only the central 20 percent of the base area) produced both the largest wall excess temperature and the lowest CHF of all the heat flux distributions investigated, due to the flow maldistribution induced. A single transverse hotspot spanning the heat sink perpendicular to the flow direction resulted in different CHF values based on its streamwise location; CHF was largest when the hotspot was placed nearest the inlet and smallest when placed nearest the outlet. The visualizations revealed that CHF occurs when there is a sudden and unalleviated upstream expansion of vapor in one or more channels above the hotspot, causing the local wall temperature to rapidly increase. The proximity of the hotspot to the inlet manifold, which communicates between all channels and can relieve downstream vapor expansion, appears to determine the resiliency of the heat sink to conditions leading to CHF.