The effects of using aqueous nanofluids containing covalently functionalized graphene nanoplatelets with triethanolamine (TEA-GNPs) as novel working fluids on the thermal performance of a flat-plate solar collector (FPSC) have been investigated. Water-based nanofluids with weight concentrations of 0.025%, 0.05%, 0.075%, and 0.1% of TEA-GNPs with specific surface areas of 300, 500, and 750 m2/g were prepared. An experimental setup was designed and built and a simulation program using MATLAB was developed. Experimental tests were performed using inlet fluid temperatures of 30, 40, and 50 °C; flow rates of 0.6, 1.0, and 1.4 kg/min; and heat flux intensities of 600, 800, and 1000 W/m2. The FPSC’s efficiency increased as the flow rate and heat flux intensity increased, and decreased as inlet fluid temperature increased. When using nanofluids in the FPSC, the measured temperatures of absorber plate and tube wall decreased down to 3.35% and 3.51%, respectively, with the increase in weight concentration and specific surface area, while the efficiency increased up to 10.53% for 0.1- wt% TEA-GNPs nanofluid with specific surface area of 750 m2/g, in comparison with water. When using water as heat transfer fluid, very good agreement was obtained between the experimental and predicted values of absorber plate temperature, tube wall temperature, and collector’s efficiency with maximum differences of 3.02%, 3.19%, and 3.26%, respectively. While, when using nanofluids, higher differences were found, up to 4.74%, 4.7%, and 13.47% for TEA-GNPs nanofluid with specific surface area of 750 m2/g, respectively. Accordingly, the MATLAB code was capable of simulating the thermal performance of FPSCs utilizing nanofluids as their heat transfer fluids with acceptable accuracy. Values of performance index were all greater than 1, and increased as weight concentration increased up to 1.104 for 0.1- wt% TEA-GNPs nanofluid with specific surface area of 750 m2/g, implying higher positive effects on efficiency than negative effects on pressure drop. Accordingly, the investigated nanofluids can efficiently be used in FPSCs for enhanced energy efficiency, and the 0.1- wt% water-based TEA-GNPs nanofluid with specific surface area of 750 m2/g was comparatively the superior one.