To be 'raising Cain' is to be causing trouble or creating an uproar.
Cain was the first murderer according to scriptural accounts in the Bible - Genesis 4 and in the Qur'an - 5:27-32. The biblical account, from the King James' Version, tells of how Cain and Abel, the two sons of Adam and Eve, bring offerings to God, but only Abel's is accepted. Cain kills Abel in anger and is cursed by God:
4:1 And Adam knew Eve his wife; and she conceived, and bare Cain, and said, I have gotten a man from the LORD.
4:2 And she again bare his brother Abel. And Abel was a keeper of sheep, but Cain was a tiller of the ground.
4:3 And in process of time it came to pass, that Cain brought of the fruit of the ground an offering unto the LORD.
4:4 And Abel, he also brought of the firstlings of his flock and of the fat thereof. And the LORD had respect unto Abel and to his offering:
4:5 But unto Cain and to his offering he had not respect. And Cain was very wroth, and his countenance fell.
4:6 And the LORD said unto Cain, Why art thou wroth? and why is thy countenance fallen?
4:7 If thou doest well, shalt thou not be accepted? and if thou doest not well, sin lieth at the door. And unto thee shall be his desire, and thou shalt rule over him.
4:8 And Cain talked with Abel his brother: and it came to pass, when they were in the field, that Cain rose up against Abel his brother, and slew him.
4:9 And the LORD said unto Cain, Where is Abel thy brother? And he said, I know not: Am I my brother's keeper?
The transitive verb 'to raise' has been used since at least the 14th century to mean 'to conjure up; to cause a spirit to appear by means of incantations'. Geoffrey Chaucer made use of that meaning in The Canon's Yeoman's Tale, circa 1395:
I haue yow told ynowe To reyse a feend al looke he neuere so rowe.
In Modern English - [I have told you enough already to raise a fiend, look he never so savage.]
If you make trouble you are raising, i.e. conjuring up, the accursed spirit of Cain. This is similar to several phrases that allude to calling-up or 'raising' the Devil. There's 'raise the Devil' of course and also 'raise hob' and 'raise hell'.
The phrase is American and is first found there in the late 19th century; for example, this little pun on the word 'raised' from the St. Louis' Daily Pennant, May 1840:
"Why have we every reason to believe that Adam and Eve were both rowdies? Because they both raised Cain."