A rapid, simple, selective and highly sensitive simultaneous determination of Cu(II) and Pb(II) via newly fashioned 5,11,17,23-tetra-tert-butyl-25,27-dihydrazinamidecarbonylmethoxy-26,28-dihydroxycalix[4]arene-grafted multi-walled carbon nanotubes-modified carbon paste electrode (CNT-Calix/CPE) by differential pulse anodic stripping voltammetry (DPASV) has been introduced. It was observed that CNT-Calix/CPE exhibits higher selectivity and stability for Cu(II) and Pb(II). Different operational parameters such as pH, deposition potential/time, pulse amplitude (5, −1.0 V vs. Ag/AgCl, 300 s, 2 s, 0.05 V) were also optimized for calculation and statistical evaluation of linear range, detection limit and limit of quantification. Interference study shows that the electrode is highly selective for the simultaneous determination of Cu(II) and Pb(II). Standard addition method was used to apply CNT-Calix/CPE in waste water, plant leaves and soft drinks and it was found that the concentration of Cu(II) and Pb(II) were corresponding to standardized values.