A new synthetic approach to tri-substituted trisalkoxy-hexavanadate clusters containing different organic groups was developed in this work. Four mixed-valence or fully reduced POV hybrids were synthesized and structurally characterized, including an amino-containing derivative of hexavanadate, Na2[VVO10{NH2C(CH2O)3}3] (1). Furthermore, a novel mixed-valence POV hybrid was prepared via the amidation of 1, indicating that 1 can be used as an excellent building block for the design and synthesis of mixed-valence POV functional materials.