Of American-English origin, the phrase to raise Cain means to create trouble or a commotion.

In the Old Testament, Cain is the name of the eldest son of Adam and Eve, and murderer of his brother Abel. This phrase is a euphemism for synonymous idiomatic expressions such as to raise the Devil, to raise hell and to raise (Old) Ned; this is clear in the second-earliest instance of to raise Cain that I have found, from the Maumee City Express (Maumee City, Ohio) of Saturday 16^th May 1840:

Why have we every reason to believe that Adam and Eve were both rowdies? Because Eve raised the Old Harry¹, and they both raised Cain.

¹ Old Harry: a familiar name for the Devil

Phrases such as to raise the Old Harry, to raise the Devil and to raise hell allude in turn to the literal use of raise in the sense to cause (a spirit, demon, ghost, etc.) to appear, especially by means of incantations. This literal use is first recorded in The Canon’s Yeoman’s Tale, by the English poet Geoffrey Chaucer (circa 1342-1400):

As I trowe, I have yow toold ynowe
To reyse a feend.
     in contemporary English:
As I believe, I have told you enough
To raise a fiend.

The earliest instance of to raise Cain that I have found is from the correspondence from New York, dated Monday 6^th April 1840, published in The Daily Picayune (New Orleans, Louisiana) on Saturday the 18^th of the same month:

The Irishmen at the Croton Water Works are raising Cain once more. Two companies have been ordered to the scene of action this morning to prevent mischief—the workmen threatening to destroy the works and shellalah² any body who attempts to prevent their righteous operations.

² to beat with a shillelagh (shillelagh: a cudgel of blackthorn or oak – from the name of a barony and village in County Wicklow, Ireland)

The phrase to raise Cain had appeared earlier as a pun recorded in The Burlington Free Press (Burlington, Vermont) of Friday 26^th July 1833:

Finn’s Comical Concert.—Mr. Finn served up a rich entertainment of fun, to a respectable audience, who assembled last evening, for the sole purpose of enjoying the luxury of excessive mirth.
His performances were welcomed with sounds of applause. He gave the following conundrums.
Why is this village like a mouse in a cat’s paw. Because Paw-tucket.
Why were factories like temperance societies. Because they go by water.
Why were Adam and Eve Sugar Planters.
D’ye give it up.—Because they raised Cain—(cane.)
[&c.]