Relatively little research has been conducted to systematically quantify the nationwide earthquake risk of gas pipelines in the US; simultaneously, national guidance is limited for operators across the country to consistently evaluate the earthquake risk of their assets. Furthermore, many challenges and uncertainties exist in a comprehensive seismic risk assessment of gas pipelines. As a first stage in a systematic nationwide assessment, we quantify the earthquake risk of gas transmission pipelines in the conterminous US due to strong ground shaking, including the associated uncertainties. Specifically, we integrate the US Geological Survey 2018 National Seismic Hazard Model, a logic tree–based exposure model, three different vulnerability models, and a consequence model. The results enable comparison against other risk assessment efforts, encourage more transparent deliberation regarding alternative approaches, and facilitate decisions on potentially assessing localized risks due to ground failures that require site-specific data. Based on the uncertainties approximated herein, the resulting sensitivity analyses suggest that the vulnerability model is the most influential source of uncertainty. Finally, we highlight research needs such as (1) developing more vulnerability models for regional seismic risk assessment of gas pipelines; (2) identifying, prioritizing, and measuring input pipeline attributes that are important for estimating seismic damage; and (3) better quantifying seismic hazards with their uncertainties at the national scale, for both ground failures and ground shaking.