The present work investigated the possibility to use wet blue (WB) leather wastes as natural reinforcing fibers within different polymer matrices. After their preparation and characterization, WB fibers were melt-mixed at 10 wt.% with poly(lactic acid) (PLA), polyamide 12 (PA12), thermoplastic elastomer (TPE), and thermoplastic polyurethane (TPU), and the obtained samples were subjected to rheological, thermal, thermo-mechanical, and viscoelastic analyses. In parallel, morphological properties such as fiber distribution and dispersion, fiber–matrix adhesion, and fiber exfoliation phenomena were analyzed through a scanning electron microscope (SEM) and energy-dispersive spectroscopy (EDS) to evaluate the relationship between the compounding process, mechanical responses, and morphological parameters. The PLA-based composite exhibited the best results since the Young modulus (+18%), tensile strength (+1.5%), impact (+10%), and creep (+5%) resistance were simultaneously enhanced by the addition of WB fibers, which were well dispersed and distributed in and significantly branched and interlocked with the polymer matrix. PA12- and TPU-based formulations showed a positive behavior (around +47% of the Young modulus and +40% of creep resistance) even if the not-optimal fiber–matrix adhesion and/or the poor de-fibration of WB slightly lowered the tensile strength and elongation at break. Finally, the TPE-based sample exhibited the worst performance because of the poor affinity between hydrophilic WB fibers and the hydrophobic polymer matrix.