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In the present paper, we provide evidence of the vital impact of inertia on the flow in microfluidic networks, which is disclosed by the appearance of nonlinear velocity–pressure coupling. The experiments and numerical analysis of microfluidic junctions within the range of moderate Reynolds number (1 < Re < 250) revealed that inertial effects are of high relevance when Re > 10. Thus, our results estimate the applicability limit of the linear relationship between the flow rate and pressure drop in channels, commonly described by the so-called hydraulic resistance. Herein, we show that neglecting the nonlinear in their nature inertial effects can make such linear resistance-based approximation mistaken for the network operating beyond Re < 10. In the course of our research, we investigated the distribution of flows in connections of three channels in two flow modes. In the splitting mode, the flow from a common channel divides between two outputs, while in the merging mode, streams from two channels join together in a common duct. We tested a wide range of junction geometries characterized by parameters such as: (1) the angle between bifurcating channels (45°, 90°, 135° and 180°); (2) angle of the common channel relative to bifurcating channels (varied within the available range); (3) ratio of lengths of bifurcating channels (up to 8). The research revealed that the inertial effects strongly depend on angles between the channels. Additionally, we observed substantial differences between the distributions of flows in the splitting and merging modes in the same geometries, which reflects the non-reversibility of the motion of an inertial fluid. The promising aspect of our research is that for some combinations of both lengths and angles of the channels, the inertial contributions balance each other in such a way that the equations recover their linear character. In such an optimal configuration, the dependence on Reynolds number can be effectively mitigated.