The inferior mechanical strength and thermal resistance of foam concrete limited its application in thermal insulation engineering. This study focused on enhancing the mechanical strength and thermal resistance of foam concrete by incorporating glass lightweight microspheres (GLM) to partially replace foam. The roles of GLM in foam concrete were investigated through physical, mechanical, and thermal properties tests. The improvement mechanism behind the mechanical strength and thermal resistance was further revealed. Results indicated that the addition of GLM enhanced mechanical strength of foam concrete by promoting hydration reaction, optimizing pore structure, and improving GLM-paste interfaces. The mechanical strength of foam concrete with 20% GLM increased by about 40%. Moreover, GLM improved the residual compressive strength after exposure to 800°C, with an enhancement of 39.8%. The inclusion of GLM reduced the risks of crack formation, densified the paste, and strengthened the foam wall due to its hollow structure, pozzolanic reactivity, melting and filling effects, and the phase transformation of additional C-S-H into well-packed wollastonite. Additionally, GLM with closed and isolated pores reduced the drying shrinkage and water absorption rate of foam concrete. The finding suggests that incorporating an appropriate amount of GLM can produce high-strength, low-density, and thermal-resistant foam concrete.