early 13c., "notably large, bulky, or strong" (a sense now obsolete), from Old English mægen- "power, strength, force," used in compounds (such as mægensibb "great love," mægenbyrðen "heavy burden;" see main (n.)), probably also in part from or influenced by cognate Old Norse megenn (adj.) "strong, powerful, mighty."
Sense of "chief, principal, prime" is from c. 1400. That of "principal or chief in size or extent" is from 1590s. Main chance "opportunity of enriching oneself" is by 1570s, from the game of hazard. Main course in the meal sense attested from 1829. Main man "favorite male friend; hero" is by 1967, African-American vernacular.
c. 1200, afote, "on foot, walking, not on horseback," contraction of prepositional phrase on fotum; see a- (1) "on" + foot (n.). Meaning "astir, on the move" is from 1520s; figurative sense of "in active operation" is from 1601 ("Julius Caesar").