The paper presents the results of research on liquid flow maldistribution in the shell side of a shell-and-tube heat exchanger (STHE). This phenomenon constitutes the reason for the formation of the velocity reduction area and adversely affects heat transfer and pressure drop. In order to provide details of the liquid distribution in STHE, two visualization methods were utilized. First, computational fluid dynamics (CFD) code coupled with the k-ε model and the laser-based particle image velocimetry (PIV) technique was applied. The tests were carried out for a bundle comprising 37 tubes in an in-line layout with a pitch dz/t = 1.5, placed in a shell with Din = 0.1 m. The STHE liquid feed rates corresponded to Reynolds numbers Rein equal to 16,662, 24,993, and 33,324. The analysis demonstrated that the flow maldistribution in the investigated geometry originates the result of three main streams in the cross-section of the shell side: central stream, oblique stream, and bypass stream. For central and oblique streams, the largest velocity reduction areas were formed in the wake of the tubes. On the basis of the flow visualization, it was also shown that the in-line layout of the tube bundle helps to boost the wake region between successive tubes in a row. Additionally, unfavorable vortex phenomena between the last row of tubes and the lower part of the exchanger shell were identified in the investigations. The conducted studies confirmed the feasibility of both methods in the identification and assessment of fluid flow irregularities in STHE. The maximum error of the CFD method in comparison to the experimental methods did not exceed 7% in terms of the pressure drops and 11% in the range of the maximum velocities.