In the U.S. the KEITHLEY and KEITHLY families can be loosely divided into two groups: German and English.
The German branch (both KEITHLEY and KEITHLY) is generally thought to have first come to North America around 1775 from the Rhineland, the German/Denmark border, or less likely, Holland. possibly through the port at Philadelphia, and probably with a more germanic spelling of the name, e.g. Kuechle or Kicheli.
There is some evidence that they settled along Blanket Bottom Creek in what was then Rowan County in present day North Carolina, where they were neighbors of Squire Boone, Daniel Boone's father. They soon migrated west, eventually settling in Kentucky, southern Indiana, Illinois, Missouri, Nebraska, etc.
Even the English KEITHLEYs trace their lineage to Germany. The College of Arms in London acknowledges the Catti tribe from the area now known as Hesse-Cassel in Germany as the origin. The Catti emigrated to Holland, and to northern Britain. Descendents of the Catti include names like Kethi, Keth, Keith, Keighley, Keightley; and the Chattan Clan, which includes the MacPhersons and Sutherlands. However, to date no one has been able to prove a connection between the English and German families.
Frank DEIS has write-ups on the German KEITHLEY/KEITHLY family at german and Maryland/English KEITHLEY family at english.