Circulating tumor cells (CTCs), crucial biomarkers for monitoring cancer metastasis and prognosis, present significant challenges for detection technologies due to their extremely low abundance in peripheral blood. This study introduces a low-field nuclear magnetic resonance (LF-NMR) biosensor leveraging the synergistic effect of biorthogonal chemistry and click chemistry for CTC detection by a sol-gel phase-transition strategy. Initially, CTCs were targeted and enriched using mucin 1-specific aptamers. Subsequently, Cys-GO@CuO nanoprobes were assembled quantitatively on captured CTCs through target-triggered bioorthogonal chemistry: sialic acid molecules on the cell membrane were oxidized by NaIO4 to generate aldehyde groups, enabling their covalent coupling with thiol/amino groups of nanoprobes via thiazolidine bond formation. Then, acidolysis reduction of CuO released Cu+ ions, catalyzing azide-alkyne cycloaddition click reactions to drive sol-gel phase transitions. Quantitative CTC analysis was achieved by monitoring LF-NMR-derived transverse relaxation time (T2) signal changes. Under optimal conditions, the detection limit for MCF-7 cells is as low as 5 cells/mL, with satisfactory precision and accuracy for real samples. This integrated platform offers a sensitive, accurate, stable, and operationally simple method for CTC detection, showcasing promising applications for liquid biopsy and precision medicine.