Materials from renewable resources have attracted attention due to their high availability, biodegradability, environment-friendly characteristics and competition with fossil sources. Natural rubber latex (NRL) and lignin are promising renewable materials with dissimilar characteristics, such as hydrophobicity and high phenolic group content, respectively, making them interesting for adhesive applications. However, the combination to form an adhesive is still poorly explored in the literature. In this work, we aimed to develop a water-based and a more sustainable adhesive based on LBN and lignin additivation. In this context, the nanoscale interaction between LBN and three types of lignin from different pretreatments (organosolv, alkali and Kraft) was investigated by atomic force microscopy (AFM), revealing an intrinsic interaction with NRL according to the lignin extraction route. The mechanical properties of NRL-lignin adhesive films reproduced the nanoscale interaction observed by AFM, suggesting an ideal lignin’s extraction route for NRL additivation, which can be used to join different materials with this optimized adhesive formulation. The evaluation of colloidal properties indicated the solubilization of lignin in LBN, evidencing the chemical compatibility between the components, with stability of around 50 days. As a proof-of-concept, several substrates were adhered to each other by pressure using the selected lignin (via alkali route) in NRL water-based adhesive. The shear mechanical tests of adhered substrates showed superior performance with dried and underwater NRL-lignin joints compared to neat NRL. The adhesion on different substrates was improved by 200%, 74%, 71% and 27% on glass, aluminum, polypropylene (PP) and wood substrates, respectively, in dry conditions. The adhesive also displayed improved performance compared to some commercial adhesives on PP substrates. These findings reveal the versatility of NRL-lignin formulated adhesives in adhering substrates with diverse degrees of hydrophobicity and porosity. Therefore, the selection of a lignin extraction route and the mechanical mixing of NRL-lignin resulted in a more sustainable adhesive with exceptional properties and great potential for commercial applications.