Defossilizing the chemical industry using air-to-chemical processes offers a promising solution to driving down the emission trajectory to net-zero by 2050. Syngas is a key intermediate in the chemical industry, which can be produced from electrolytic H2 and air-sourced CO2. To techno-economically assess possible emerging air-to-syngas routes, we develop detailed process simulations of direct air CO2 capture, proton exchange membrane water electrolysis, and CO2 electrolysis. Our results show that renewable electricity prices of ≤$15 per MW h enable the replacement of current syngas production methods with CO2 electrolysis at CO2 avoidance costs of about $200 per t-CO2. In addition, we identify necessary future advances that enable economic competition of CO2 electrolysis with traditional syngas production methods, including a reverse water gas shift. Indeed, we find an improved CO2 electrolysis process (total current density = 1.5 A cm−2, CO2 single-pass conversion = 54%, and CO faradaic efficiency = 90%) that can economically compete with the reverse water gas shift at an optimal cell voltage of about 2.00 V, an electricity price of $28–42 per MW h, a CO2 capture cost of $100 per t-CO2, and CO2 taxes of $100–300 per t-CO2. Finally, we discuss the integration of the presented emerging air-to-syngas routes with variable renewable power systems and their social impacts in future deployments. This work paints a holistic picture of the targets required to economically realize a defossilized syngas production method that is in alignment with net-zero goals.