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The prediction of flow distribution in flow manifolds is important for the design of heat exchangers. The pressure drop along the flow in the header is the most influential factor in flow distribution. Various continuous models available in literature have failed to satisfactorily predict the pressure distribution in the headers of the flow manifolds. In this article, a discrete model matching the real physical phenomena has been proposed, to predict the pressure distribution in headers. An experimental evaluation of relevant flow characteristic parameters has been carried out to support the discrete model calculations. The validity of the theoretical discrete model has been performed with experimental results, under specific conditions. Refined experimental probes, for pressure heads with ultrasonic measuring devices, have been used to obtain accurate results. The experimental results fully substantiate the soundness of the theoretical prediction. In addition, the advantage of the ability to accommodate local disturbances in the discrete model has been pointed out. The effect of some local disturbances may be substantial. As a result of the analysis presented in this article, improved designs of flow manifolds in heat exchangers can be realized, to assure operation safety under severe operating conditions.