Chemical composition is known to have significant effects on the grain refinement behavior of inoculated Al alloys during solidification. In this study, the influences of solute contents on the thermodynamic nucleation driving force and solid-liquid interfacial energy of binary Al alloys have been studied by CALPHAD method. The solute effect on the nucleation barrier and nucleation rate, thus on the grain refinement of Al alloys both with and without high potency nucleation particles, was analyzed based on the classical heterogeneous nucleation theory and free growth concept. Based on the classical heterogeneous nucleation theory, the calculation results reveal that Si has the effect of increasing the nucleation barrier of heterogeneous nucleation of grains and thus reduce the nucleation rate significantly. Alloying elements Cu and Mg have the effect of promoting heterogeneous nucleation and grain refinement. However, peritectic forming elements, e.g., Ti, Zr, V, have only negligible effects on the nucleation barrier. For solidification of Al alloys inoculated with high potency nucleation particles, the effect of nucleation driving force caused by different solute elements on the grain size of inoculated aluminum alloys has been quantitatively studied by a grain size prediction model for isothermal melt solidification. It is revealed that the solute dependent Gibbs-Thompson coefficients of Al-Cu, Al-Mg and Al-Si alloys have the influence of promoting the grain refinement by reducing the free growth undercooling.