The mussel-inspired catechol-based strategy has been well recognized as a promising alternative to design and exploit new generation adhesive materials applicable in many fields, ranging from biomedical adhesives to coatings of biomedical devices and engineering applications. However, in situ achievement of tough adhesion capability to substrate surfaces (e.g., minerals) is severely limited under the physiological environment or seawater condition (namely, relatively high salinity and mild alkalinity). In this work, a facile and versatile approach is proposed to in situ achieve robust wet adhesion in aqueous solutions of high salinity and mild alkalinity, via integrating primary amines into mussel-inspired polydopamine (PDA). By using a surface forces apparatus (SFA), the corresponding interaction behaviors have been systematically investigated. The strong wet adhesion was demonstrated and achieved via a synergetic effect of amine and PDA to the wet surfaces, including the surface salt displacement assisted by primary amine, strong adhesion to substrates facilitated by the catechol groups on PDA moieties, and enhanced cohesion through their cation-π interactions. Our results provide useful insights into the design and development of high-performance underwater adhesives and water-resistance materials.