As high-efficiency nanofiller for resin systems, surface functionalization of graphene oxide (GO) by introducing macromolecules has attracted enormous scientific interest. Current research on GO-based nanocomposites mainly focuses on its strong interfacial interactions with polymer matrix, but the different adsorption states of the macromolecules on the surface of GO sheets can also severely affect its reinforcement effect. Herein we concentrated on the two generally modified methods and grafted GO sheets with polyacrylamide (PAM) via facile physical adsorbing and chemical grafting routes so as to afford PAM-1, PAM-2, and PAM-3. Both the transformation procedures and the detailed interaction mechanism of products are investigated by molecular dynamic simulation combining with experiments. Besides, the PAM-modified GO nanosheets are employed as the nanofillers to improve the mechanical properties of polyimide (PI) matrix. The mechanical properties of the prepared PI-based nanocomposite films are significantly enhanced by incorporation of a small amount of chemical grafting nanosheets PAM-3 without any surface modification. In particular, compared with pure PI matrix, the addition of 0.2 wt% PAM-3 in PI can result in 78.9% increase in tensile stress and 22.4% increase in elongation at break. This article provides theoretical guidance for the choice of synthesis methods for nanofillers with high comprehensive performances.