<p>Origami honeycombs exhibit excellent designability and mechanical properties, potentially improving the bending resistance and load-bearing capacity of beams in engineering applications. In this paper, a novel origami-enhanced honeycomb sandwich beam is proposed to improve the flexural toughness and load-bearing performance. The three-point bending behavior of the origami-enhanced honeycomb sandwich beam is systematically studied. Considering the influence of loading distance, loading position, thickness gradient, and cell size, the typical panel wrinkling deformation phenomenon is observed in the origami-enhanced honeycomb sandwich beam. The origami-enhanced core improves the flexural resistance and specific energy absorption compared to traditional re-entrant honeycomb sandwich beams. It is found that the panel wrinkling phenomenon is related to the stiffness of the unit cells: larger size and greater stiffness in unit cells are more likely to induce panel wrinkling in sandwich beams. The proposed origami-enhanced honeycomb sandwich beam provides new insights for the study of flexural resistance in sandwich beams and is expected to offer significant advantages in engineering applications.</p>