Illinois Route 143 is an east–west state highway in southwestern Illinois. Its western terminus is at U.S. Route 67 (very near, but not at the termini of Illinois Route 100 and Illinois Route 140) in Alton. Its eastern terminus at Illinois Route 127 at a rural intersection west of Tamalco. This is a distance of . In 1950, it was extended west to Edwardsville. In 1964, it was extended west again to Alton, replacing Illinois Route 159. There have been no changes since.

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