It has been proved that silicon-substituted calcium phosphate ceramics possess superior bone regeneration and resorbability to HA, while the synthesis of single-phase nanocrystallized high Si-containing calcium phosphate is still a challenge. In the present work, a novel and facile aqueous precipitation method assisted with ultrasonic irradiation was adopted firstly to synthesise a single-phase nanocrystallized calcium silicophosphate (Ca5(PO4)2SiO4, CPS) biomaterial. Crystallization and morphology of Si-apatite precursors synthesized with or without ultrasonic assistance were primarily investigated and the related mechanism was discussed. Moreover, the sinterability, in vitro bioactivity and osteogenic activity of the synthesized CPS were studied in detail. Results showed that an ultrasonic cavitation effect could be beneficial to form a highly dispersive CPS precursor with a single Si-apatite phase, which greatly reduced the calcination temperature of CPS from 1350 °C to 1000 °C. Nanocrystallized CPS powders were obtained successfully under ultrasound-assisted conditions, which showed superior sinterability, in vitro bioactivity and osteogenic activity than those of micron-sized CPS and HA powders. It might be a promising candidate material for bone tissue regeneration applications.