Radioactive U(VI) in nuclear wastewater is a global environmental pollutant that poses a great threat to human health. Therefore, it is of great significance to develop a U(VI) sensor with desirable sensitivity and selectivity. Inspired by electron-donating group modification for enhancement of binding affinity toward U(VI), we report an amine group functionalization of UiO-66-NH2, using a low-cost, environmentally friendly, and low-temperature NH3 plasma technique as a fluorescence switching nanoprobe for highly sensitive and selective detection of U(VI). The resulting amine-functionalized UiO-66-NH2 (LTP@UiO-66-NH2) shows dramatically enhanced fluorescence emission and selective sensitivity for U(VI) on the basis of the quenching effect. The quenching efficiency increases from 58 to 80% with the same U(VI) concentration (17.63 μM) after NH3 plasma functionalization. As a result, the LTP@UiO-66-NH2 has the best Ksv (1.81 × 105 M-1, 298 K) and among the lowest LODs (0.08 μM, 19.04 ppb) compared with those reported in the literature. Intraday and interday precision and application in real environment experiments indicate stable and accurate U(VI) detection performance. Fluorescence lifetime and temperature-dependent detection experiments reveal that the quenching mechanism belongs to the static quenching interaction. The highly selective fluorescence detection is attributed to the selective binding of U(VI) by the rich functionalized amine groups of LTP@UiO-66-NH2. This work provides an efficient fluorescence probe for highly sensitive U(VI) detection in water, and a new strategy of tailored plasma functionalization for developing a practical MOF sensor platform for enhanced fluorescence emission, sensitivity, and selectivity for detecting trace amounts of radioactive species in the environment.