In this work, the photocatalytic activity of nanoparticles (NPs) of zinc oxide synthetized by Prosopis laevigata as a stabilizing agent was evaluated in the degradation of methylene blue (MB) dye under UV radiation. The theoretical study of the photocatalytic degradation process was carried out by a Langmuir–Hinshelwood–Hougen–Watson (LHHW) model. Zinc oxide nanoparticles were synthesized by varying the concentration of natural extract of Prosopis laevigata from 1, 2, and 4% (weight/volume), identifying the samples as ZnO_PL1%, ZnO_PL2%, and ZnO_PL4%, respectively. The characterization of the nanoparticles was carried out by Fourier transform infrared spectroscopy (FT-IR), where the absorption band for the Zn-O vibration at 400 cm−1 was presented; by ultraviolet–visible spectroscopy (UV–vis) the value of the band gap was calculated, resulting in 2.80, 2.74 and 2.63 eV for the samples ZnO_PL1%, ZnO_PL2%, and ZnO_PL4%, respectively; XRD analysis indicated that the nanoparticles have a hexagonal zincite crystal structure with an average crystal size of 55, 50, and 49 in the sample ZnO_PL1%, ZnO_PL2%, and ZnO_PL4%, respectively. The morphology observed by TEM showed that the nanoparticles had a hemispherical shape, and the ZnO_PL4% sample presented sizes ranging between 29 and 45 nm. The photocatalytic study showed a total degradation of the MB in 150, 120, and 60 min for the samples ZnO_PL1%, ZnO_PL2%, and ZnO_PL4%, respectively. Also, the model explains the experimental observation of the first-order kinetic model in the limit of low concentrations of dye, indicating the influence of the mass transfer processes.