Cellulose nanofibrils (CNFs) are attractive, renewable building blocks for high-performance and lightweight nanocomposites of high sustainability. Following bioinspired design principles, meaning the organization of large fractions of reinforcing CNFs in a minority matrix of suitably designed polymers, promises the best mechanical performance. However, thus far, truly synergetic mechanical behavior in such nanocomposites—as often found in biological load-bearing tissues—with a simultaneous increase of stiffness, toughness, and strength have remained elusive. Here we describe such a system realizing outstanding synergies in the relevant mechanical performance indicators by combining anionic TEMPO-oxidized CNFs with a self-cross-linkable PU resin. Strikingly, appropriate counterion selection, that is, an exchange of the commonly used sodium to the large tetrabutyl ammonium, turns out to be of key importance to tailor the interaction between the components in a suitable fashion. Ultimately, at only 10 wt % of PU, the cured nanocomposites achieve twice as high stiffness, yield strength, toughness, and strength than a pure CNF nanopaper, allowing the nanocomposites to reach close to 20 GPa in stiffness, 450 MPa in tensile strength at ca. 14% strain. The resulting materials are located in previously completely unoccupied territories in mechanical properties for waterborne CNF/polymer nanocomposites. The study shows that subtle engineering of interactions and attractive PUs containing various noncovalent interaction motifs provide unforeseen opportunities in reaching remarkable mechanical property areas in bioinspired nanocomposites which are promising in applications for future lightweight high-performance sustainable materials.