In this work, it is presented for the first time that nitrogen and chlorine co-doped carbon nanodots (N,Cl-CDs) were synthesized by simply mixing glucose, concentrated hydrochloric acid (HCl), and 1,2-ethylenediamine (EDA). No external heat was employed; the neutralization reaction served as the heat source. The glucose served as the carbon source while EDA and HCl were the N and Cl dopants, respectively. The fluorescence of N,Cl-CDs was adequately quenched by hexavalent chromium Cr(VI) based on a combination of dynamic quenching and inner filter effect (IFE). Accordingly, an efficient N,Cl-CDs-based fluorescence probe was established for sensitive and selective detection of Cr(VI). The proposed fluorescence sensor provides a linear recognition range for Cr(VI) determination from 3 to 40 µM with a limit of detection (LOD) of 0.28 µM (14.6 µg/L). The proposed fluorescence method was successfully utilized to detect Cr(VI) in different water samples with satisfactory results. The spike recoveries vary from 97.01% to 103.89% with relative standard deviations (RSDs) of less than 0.82%. This work highlights the development of a simple, ultrafast, and energy-saving one-step synthetic route to fabricate N,Cl-CDs for highly selective and sensitive detection of Cr(VI) in real water samples. It is anticipated that the proposed fluorescence method could be further explored and widely used for Cr(VI) detection in the environmental industry.