Lead-zinc mine tailing waste can have significant environmental impacts due to its potential for releasing toxic elements into the surroundings and contaminating local soil and water. This paper focuses on the valorization of lead-zinc mine tailing waste through geopolymerization, a sustainable process that can transform waste into useful building materials. Geopolymer matrixes with various mixtures of mine tailing (0−100 wt%), fly ash (0−100 wt%), and flue gas desulfurization (FGD) gypsum (0, 5, and 10 wt%) were synthesized using different activators such as sodium hydroxide (NaOH, 5, 10 M) and sodium silicate (waterglass, 0, 12.5 wt%). Visual inspection, unconfined compressive strength (UCS) testing, and microstructural analysis (e.g., X-ray diffractions, Fourier transforms infrared, and scanning electron microscopy) were employed for the physicochemical characterization of these geopolymers. The highest UCS value of 24.1 MPa was observed in a geopolymer specimen with 100 wt% fly ash and activated by 10 M NaOH and cured for 28 days. The blending of mine tailings would result in strength recession, e.g., the integrating of 25 wt% tailings showed a UCS of 12.3 MPa. The addition of 5 wt% gypsums can improve early strength development, particularly for matrixes with 50–75 wt% fly ash. But adding 10 wt% gypsums would lead to strength retrogression of the resulting geopolymers. The introduction of waterglass can also facilitate geopolymerization and improve strength development. However, the cointegrating of gypsum and waterglass can induce an antagonistic effect and lead to the collapse of the geopolymer specimens. The findings revealed that the strength and microstructural properties of geopolymer are determined by the matrix compositions, alkaline activators, etc. Effective regulation of these factors can produce geopolymer matrixes with high dimensional stability and UCS that well meet construction material standards. Overall, the study indicates that geopolymerization represents a viable and eco-friendly solution for valorizing lead-zinc mine tailing waste and gaining alternative building materials.