Cu-functionalized mesoporous MCM-41 materials were synthesized via two different types of post-functionalization modification of MCM-41, without the ligand (MCM-41@Cu) and with ligand (MCM-41@Histidine@Cu). Cu-functionalized mesoporous MCM-41 sample was also prepared directly via co-condensation of CuCl2 and decyltrimethylammonium bromide (DTAB) with tetraethyl orthosilicate (TEOS) (Cu-MCM-41). The textural properties of the samples were characterized by powder X-ray diffraction (XRD), Fourier transforms infrared (FTIR) spectra, nitrogen adsorption–desorption, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The results show that the structure of MCM-41 persisted after modification. These catalysts are efficient catalysts for the synthesis of 5-substituted 1H-tetrazoles in water. Cu-functionalized mesoporous MCM-41 materials displayed high catalytic performance at low-temperature. Cu-functionalized MCM-41 sample synthesized with direct co-condensation method displayed better catalytic activity compared to Cu-functionalized mesoporous MCM-41 materials prepared with post-synthesis grafting methods. These catalysts can be easily recovered.