With rising interior air pollution, health, and food shortage concerns, wood adhesives derived from non-food sustainable materials have therefore attracted considerable attention. Here we developed an eco-friendly cottonseed-lignin adhesive consisting of non-food defatted cottonseed flour (DCF), alkali lignin (AL), and graphene oxide (GO). The cation-π interaction, and hydrogen and covalent bonds between AL@GO and DCF collectively enhanced the cross-linking structure of the cured cottonseed-lignin adhesive, based on the Fourier-transform infrared spectroscopy, thermogravimetric analyses, scanning electron microscopy, and sol-gel tests. The high performance of the developed cottonseed-lignin adhesive was evidenced by its increased wet/dry shear strength and decreased rheological properties before curing and improved thermal stability and decreased soluble substances after curing. Particularly, the highest wet shear strength of poplar plywood bonded with cottonseed-lignin adhesive was 1.08 MPa, which increased by 74.2 and 54.3% as compared to the control and requirement of the Chinese standard GB/T 9846-2015 for interior plywood (≥0.7 MPa), respectively. The technology and resultant adhesives showed great potential in the preparation of green woody composites for many applications.