This work analyzes the interaction between non-equilibrium plasma and detonation. The aim is to enhance the detonability of gaseous mixtures by reducing the detonation cell width through dissociation of a fresh gas mixture by plasma action. The experiments were performed in a square-section detonation tube, and the diagnostic tools used were ICCD chemiluminescence imaging, soot-plate recording, dynamic pressure sensors, and back current shunt technique. The results show that the application of a nanosecond plasma ahead of a self-sustained detonation reduces the cell width by a factor of about 2 in H2:O2:Ar, H2:O2, CH4:H2:O2:Ar and CH4:O2:Ar mixtures for initial pressures between 100 and 200 mbar. A parametric study of plasma properties focused on the effect of the initial pressure on the deposited energy and homogeneity. A kinetic mechanism was proposed to estimate the dissociation effect of plasma chemistry on the fresh combustible mixture. The obtained densities of atoms produced in the plasma were used as input parameters to calculate the thermicity and temperature profiles of the detonation reaction zone according to the Zel’dovich-von Neumann-D¨oring model. The reduction factor of the ZND characteristic chemical length is about the same as the experimental cell widths, i.e. 2. This combination of experiments and calculations substantiates the relationship between plasma parameters, ZND chemical lengths, and detonation cell widths and, thus, demonstrates the possibility of controlling detonability using a nanosecond discharge.