In the context of the rapid development of low-carbon economy, there has been increasing interest in utilizing naturally abundant and cost-effective one-carbon (C1) substrates for sustainable production of chemicals and fuels. Moorella thermoacetica, a model acetogenic bacterium, has attracted significant attention due to its ability to utilize carbon dioxide (CO2) and carbon monoxide (CO) via the Wood–Ljungdahl (WL) pathway, thereby showing great potential for the utilization of C1 gases. However, natural strains of M. thermoacetica are not yet fully suitable for industrial applications due to their limitations in carbon assimilation and conversion efficiency as well as limited product range. Over the past decade, progresses have been made in the development of genetic tools for M. thermoacetica, accelerating the understanding and modification of this acetogen. Here, we summarize the physiological and metabolic characteristics of M. thermoacetica and review the recent advances in engineering this bacterium. Finally, we propose the future directions for exploring the real potential of M. thermoacetica in industrial applications.