Three-dimensional concrete printing (3DCP) can proliferate the industrialization of the construction sector, which is notoriously conservative and indolent toward changes. However, the mechanical behavior of 3DCP should be characterized and modeled considering the interfaces when its performance is thoroughly compared to that of the existing concrete construction methods. This study presents an experimental and numerical investigation of uniaxial compression and three-point bending (TPB) tests on extruded 3DCP beams in different loading directions. The orientation of translational and depositional interfaces with respect to the direction of loading influenced the strength. Both the elastic and post-damage behavior of the 3DCP specimens were compared with those of the conventionally cast specimen under quasi-static loading conditions. Despite the higher compressive strength of the casted specimen, the flexural strength of the 3DCP specimens was higher. This study employed the finite element and cohesive zone models of the appropriate calibrated traction-separation law to model fracture in the notched TPB specimens. Furthermore, the real-time acoustic emission test revealed the nature of failure phenomenon of three-dimensional-printed specimens under flexion, and accordingly, the cohesive law was chosen. The predicted load−displacement responses are in good agreement with the experimental results. Finally, the effects of cohesive thickness and notch shape on the performance under bending were explored through parametric studies.