Well, the internet has finally answered my question. Maptech has historical maps including our area that show (almost) exactly where 22 was. (If it says "Currently Not Available", try hitting reload.) The 1939 editions, in particular, reveal that US 22 leaves Bethlehem on Easton Ave. In between, it seems that US 22 used Main St and/or New St to get between Union and Elizabeth.
I coupled these maps with AutoStitch to create full quadrangle historical maps. Now to find a nice large-format printer. Or should I just buy them from Maptech?