We described a regioselective synthesis of two 1-(arylsulfonyl)-1H-1,2,4-triazol-5-amines 17 with good yields through a triethylamine-mediated N-sulfonylation reaction of 1H-1,2,4-triazol-5-amine 15 with arylsulfonyl chlorides 16 in dichloromethane at ambient temperature for 3 h. The N-heterocyclic sulfonamides 17 were characterized by spectroscopy, mass spectrometry, thermal analysis, and single crystal X-ray diffraction (SC-XRD). The SC-XRD analysis showed that compounds 17a and 17b have layered molecular structures, which are assembled through short hydrogen bonds involving N-H‧‧‧N, N-H‧‧‧O, C-H‧‧‧O, and C-H‧‧‧π, and interconnected by π‧‧‧π stacking interactions. For the two triazoles, electrostatic forces are the dominant attracting force within the molecular sheets, while dispersion forces play a more predominant role between the sheets. The packing arrangements were studied by crystallographic analysis and complementarily through computational calculations. Finally, these sulfonamides 17a and 17b demonstrated the most promising in vitro anticancer activity against the SNB-75 and UO-31 cell lines associated with the central nervous system and renal cancer, exhibiting moderate growth inhibition percentages of 18.7 % and 27.2 %, respectively.