Nanodiamonds (NDs) with nitrogen vacancy (NV) color centers have the potential for quantum information science and bioimaging due to their stable and non-classical photon emission at room temperature. Large-scale fabrication of molecular-size nanodiamonds with sufficient color centers may economically promote their application in versatile multidisciplinary fields. Here, the manufacture of molecular-size NV center-enriched nanodiamonds from graphite powder is reported. We use an ultrafast laser shocking technique to generate intense plasma, which transforms graphite to nanodiamonds under the confinement layer. Molecular dynamics simulations suggest that the high pressure of 35 GPa and the high temperature of 3,000K result in the metaphase transition of graphite to nanodiamonds within 100 ps. A high concentration of NV centers is observed at the optimal laser energy of 3.82 GW/cm 2 , at which point molecular-size (∼5 nm) nanodiamonds can individually host as many as 100 NV centers. Consecutive melamine annealing following ultrafast laser shocking enriches the number of NV centers >10-fold and enhances the spontaneous decay rate of the NV center by up to 5 times. Our work may enhance the feasibility of nanodiamonds for applications, including quantum information, electromagnetic sensing, bioimaging, and drug delivery. Ultrafast laser shock is used to transform graphite to nanodiamonds at ambient conditions The nanodiamonds can individually host ∼100 NV centers Annealing greatly enriches number of NV centers and enhances spontaneous decay rate Motlag et al. describe an ultrafast laser shocking technique to obtain ultrahigh concentrations of color centers in nanodiamonds (∼5 nm) under ambient conditions. Each nanodiamond can individually host ∼100 NV centers, which is orders of magnitude higher than the state of the art.