Highly selective extraction of uranium from seawater is currently extremely challenging. Although the amidoxime group (HAO) is the commonly used ligand in seawater uranium extraction, it also has strong binding capacity for vanadium ion. It has been shown that the introduction of phosphate groups into amidoxime-based adsorbents can improve the adsorption performance of materials through a synergistic effect between functional groups. In this work, we have systematically investigated the selective extraction behavior of the phosphate ligand (methylphosphonic acid, HL1) for uranyl cation and the synergistic effect with amidoxime using density functional theory (DFT). The electron-donor-substituted derivatives of HL1 (aminomethylphosphonic acid (HL2) and methyl phosphate (HL3)) were also considered. Not unexpectedly, the results show that introduction of HL1 into the amidoxime-based adsorbents improves the extraction and selectivity for uranyl cations. This is mainly due to the fact that HL1 is more likely to deprotonate, which promotes the dissociation of [UO2(CO3)3]4-, and the presence of the phosphate groups in the synergistic complexes alters the optimal coordination mode of VO2+. In addition, the HL2 and HL3 ligands further improve the uranium extraction performance, especially for HL3. This work provides guidelines for the rational design of sequestering ligands for uranium extraction from seawater.