South-west of St Louis, a section of Interstate 44 was closed by flooding near the town of Rolla while part of Interstate 70 was also closed in the neighbouring state of Illinois.
Many other smaller roads were also closed across the two states, where flood warnings were in effect.
Floods also inundated a wastewater treatment plant south of St Louis on Monday, causing sewage to flow directly into rivers and streams.
The flooding in Missouri and southern Illinois began over the weekend after as much as 10ins (25cm) of rain fell in some areas in a matter of hours.
It came after severe storms over the Christmas holiday claimed at least 49 lives across southern and western states of the US.
Parts of eastern Oklahoma, Arkansas and Illinois are still subject to flood warnings.
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