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Fresno, California, population 509,039 (2010 census), is the largest city in the United States that is not on any Interstate highway. Fresno is on the CA-99 freeway, but not on any Interstate.

San Jose, California, population 945,942 (2010 census), is the largest city in the United States that is not on any primary Interstate highway (i.e., numbers 1 to 99). San Jose is on I-280, I-680, and I-880.

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Q: What are the largest cities not built on a waterway in the US?
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