With the convenient and fast requirements for construction in bridge engineering, prefabricated assembly technology is widely applied in engineering construction. Typically, prefabricated bridge decks are connected through cast-in-place wet joints. Wet joints, as the primary load-bearing parts of bridge decks, undergo complex stress and are prone to cracking and damage. Particularly in the negative bending moment region of bridges, the influence of tensile stress on wet joints is more severe, thus enhancing the mechanical performance and crack resistance of joints becomes crucial. This paper investigates the mechanical behavior of prefabricated reinforced concrete bridge deck panels with variable cross-sections under negative bending moments, focusing on the performance of Ultra High-Performance Concrete (UHPC) wet joints. Full-scale experimental tests were conducted on a 176 m steel truss composite continuous rigid bridge, employing C50 concrete panels with UHPC wet joints. Results show three distinct stages: elastic, crack initiation and propagation, and failure. The maximum failure load reached 822 kN, with a maximum displacement of 21.64 mm. Concrete strains indicate compressive stress near the wet joint and tensile stress near the loading positions. Cracks primarily develop at the wet joint interface and propagate under increasing load, ultimately leading to flexural–shear failure near the variable cross-section of the wet joint. Numerical simulations using ABAQUS/CAE (2020) corroborate experimental findings, closely matching load-displacement curves and identifying damage locations. The study demonstrates that UHPC wet joints significantly enhance crack resistance, meeting design requirements for improved mechanical performance in bridge structures subjected to negative bending moments.