Using natural gas as a fuel in the road freight sector instead of diesel could cut greenhouse gas and air quality emissions but the switch alone is not enough to meet UK climate targets. A life cycle assessment (LCA) has been conducted comparing natural gas trucks to diesel, biodiesel, dimethyl ether and electric trucks on impacts to climate change, land use change, air quality, human health and resource depletion. This is the first LCA to consider a full suite of environmental impacts and is the first study to estimate what impact natural gas could have on reducing emissions form the UK freight sector. If LNG is used, climate change impacts could be up to 33% lower per km and up to 12% lower per kWh engine output. However, methane emissions will eliminate any benefits if they exceed 1.5–3.5% of throughput for typical fuel consumption. For non-climate impacts, natural gas exhibits lower emissions (11–66%) than diesel for all indicators. Thus, for natural gas climate benefits are modest. However, emissions of CO, methane and particulate matter are over air quality limits set for UK trucks. Of the other options, electric and biodiesel trucks perform best in climate change, but are the worst with respect to land use change (which could have significant impacts on overall climate change benefits), air quality, human toxicity and metals depletion indicators. Natural gas could help reduce the sector's emissions but deeper decarbonization options are required to meet 2030 climate targets, thus the window for beneficial utilisation is short.