Wheat storage proteins are the key to the functionality and end-use properties of wheat. The structural properties of the storage proteins and their ability to cross-link determine the functionality of the wheat flour for different products. We have investigated the structural properties of wheat storage proteins and their cross-linking behavior utilizing experimental methods, primarily HPLC, coarse-grained modeling and Monte Carlo simulations, and prediction algorithms on gliadin-rich fraction, in vitro produced α-gliadins, and synthetic gliadin peptides. Our results showed that the gluten proteins were intrinsically disordered with mostly turns and loops and a “self-avoiding walk” behavior in water. Hydrophobicity of neighboring peptide sections, synthesis chronology, and amino acid chain flexibility were identified as important factors, determining if intra- or intermolecular disulfide bonds should be formed in or between the wheat storage proteins and subunits. The level of the liquid state impacted the polymerization of the storage proteins, where a drier stage resulted in an increase in polymer content and size, and in β-sheet content. Polymers were predicted to be formed through cross-linking by disulfide or lanthionine bonds and through clustering by liquid-liquid phase separation. The clustering was mainly ongoing at the N-terminal part of the molecule, in particular in the presence of P- and Poly-Q sequences. The cross-linking seemed to take place in the C-terminal part of the molecule through the formation of a hydrophobic core. Thus, aggregates were formed through strong covalent bonds, gathering several wheat storage proteins in a hydrophobic core, and then weaker bonds were formed as tail-to-tail interactions. The hydrophobically driven aggregation of wheat storage proteins seems to favor cross-linking among peptide regions with high or identical amino acid composition. The present study contributes to increased knowledge of the structural properties of the wheat storage proteins and the mechanisms behind their aggregation at processing, identifies novel routes to evaluate these complex proteins, and increases the opportunities to tailor and fine-tune properties of wheat products and to tailor end-use characters in a wide array of the utilization of the proteins.