Pennsylvania Route 43 may refer to:
- U.S. Route 22 in Pennsylvania, which was signed in some segments as Pennsylvania Route 43 in the 1920s and 1930s.
- Schuylkill Expressway, which was signed as Pennsylvania Route 43 in the 1950s and 1960s, currently signed as part of Interstate 76.
- Mon–Fayette Expressway, which currently uses the Pennsylvania Route 43 designation in its non-tolled sections.
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