Chiral γ-phosphono-α-amino acids play a crucial role in inhibitors of natural enzymes, as well as agonists and antagonists of metabotropic glutamate receptors. In this paper, an efficient and general protocol for the construction of chiral γ-phosphono-α-amino acids via Pd-catalyzed AQ-directed C(sp³)–H alkylation of α-amino acid derivatives is developed. The reaction shows reactivity between methylene C(sp³)–H bonds with phosphonated alkyl iodides with high yields, enantioselectivity, and diastereomeric ratios, which enables access to a wide range of challenging and important γ-phosphono-α-amino acids in large scale. Meanwhile, δ-phosphono-α-amino acid and δ-phosphono-propionic acid derivatives can also be successfully obtained. The derivatization reaction in the synthesis of l-AP4 and l-phosphinothricin highlight the applicability of this method.