In this study, the in-situ synthesized ZrB2 nanoparticles and rare earth Sc were introduced to enhance the strength and ductility of 7N01 aluminum alloy, via the generation of high-melting and uniform nanodispersoids. The microstructure and mechanical property evolution of the prepared composites and the interaction between ZrB2 and Sc were studied in detail. The microstructure investigation shows that the introduction of rare earth scandium (Sc) can promote the distribution of ZrB2 nanoparticles, by improving their wettability to the Al melt. Meanwhile, the addition of rare earth Sc also modifies the coarse AlZnMgMnFe precipitated phases, refines the matrix grains and generates high-melting Al3(Sc, Zr)/Al3Sc nanodispersoids. Tensile tests of the composites show that with the combinatorial introduction of ZrB2 and Sc, the strength and ductility of the composites are improved simultaneously compared with the corresponding 7N01 alloy, ZrB2/7N01 composite and Sc/7N01 alloy. And the optimum contents of ZrB2 and Sc are 3 wt% and 0.2 wt% in this study. The yield strength, ultimate strength and elongation of (3 wt% ZrB2+0.2 wt% Sc)/7N01 composite are 477 MPa, 506 MPa and 9.8%, increased about 18.1%, 12.2% and 38% compared to 7N01 alloy. Furthermore, the cooperation strengthening mechanisms of ZrB2 and Sc are also discussed.