The ancestry of Route 243 is not entirely clear; some of the sources are vague or conflicting. I'll include the parts where the confidence level is high.

Imagine a flag at the intersection of today's Route 243 and Route 114 in Woodbridge. By 1940, here were the routes emanating from that intersection:

• north: Route 114, same as today
• east: also Route 114 – a former alignment (today: Route 243)
• south: SR 552, leading to Orange (today: Route 114)
• west: also SR 552, leading to Ansonia (today: Route 243)

In other words, Route 114 and SR 552 "bumped" at this intersection and did not cross.

In 1951, the state straightened out the intersection, making Route 114 continue south to Orange, and letting SR 552 continue east to New Haven.

In 1960, the state Committee to Reclassify All Public Roads recommended the following in the area:

• keep SR 552 as a state secondary highway
• add Fitch Street and Arch Street in New Haven
• remove existing Route 10 in New Haven: Dixwell Avenue, Sherman Avenue, Winthrop Avenue, and Davenport Avenue.

In 1962, SR 552 was renumbered to SR 743, since the new SR numbering system required a number in the 700s. It might have also been assigned to Fitch Street and Arch Street, extending to Dixwell Avenue. Later that year, however, "Temporary Route 10" was assigned to part of SR 743; the state was looking for a location for Route 10's southern end.

In 1963, the state figured out Route 10 for the moment, and gave SR 743 a signed route number: 243.