St. Louis served as Route 66’s main crossing point over the Mississippi River.
The highway entered Missouri from Illinois and passed through the St. Louis area before continuing west across the state. This made the city a major gateway between the eastern and western portions of Route 66.
Route 66 used bridges and urban approaches that changed over time as transportation infrastructure developed. The St. Louis region’s location on the Mississippi made it strategically important for automobile travel, commerce, and migration.
This answer is distinct from the famous Route 66 bridge at St. Louis known for its bend: the Chain of Rocks Bridge lies north of the central city and crosses the Mississippi. St. Louis is the city associated with the broader river crossing and Route 66 corridor.