by (prep.) Look up by at Dictionary.com
Old English be- (unstressed) or bi (stressed) "near, in, by, during, about," from Proto-Germanic *bi "around, about" (source also of Old Saxon and Old Frisian bi "by near," Middle Dutch bie, Dutch bij, German bei "by, at, near," Gothic bi "about"), from *umbi (cognate with second element in PIE *ambhi "around;" see ambi-).

Originally an adverbial particle of place, in which sense it is retained in place names (Whitby, Grimsby, etc.). Elliptical use for "secondary course" (opposed to main, as in byway, also compare by-blow "illegitimate child," 1590s) was in Old English. This also is the sense of the second by in the phrase by the by (1610s). By the way literally means "in passing by" (mid-14c.); used figuratively to introduce a tangential observation by 1540s.

Phrase by and by (early 14c.) originally meant "one by one," modern sense is from 1520s. By and large (1660s) originally was nautical, "sailing to the wind and off it," hence "in one direction then another;" from nautical expression large wind, one that crosses the ship's line in a favorable direction.