Why does Macbeth order the murder of Banquo and his son Fleance in Macbeth?

Macbeth's primary reason for wanting to kill Banquo and Fleance is that Macbeth fears that since the prophecies that the witches made to him have all come true, the prophecy that the witches made to Banquo, "Thou shalt get kings, though thou be none" (1.3.70), will also come true. Macbeth orders the murders of Banquo and Fleance to ensure that none of Banquo's descendants will threaten Macbeth's reign as king.

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In act 3, scene 1 of William Shakespeare's Macbeth, Macbeth explains the reason why he intends to order the murder of Banquo, his onetime friend and comrade-in-arms, and Banquo's son, Fleance.

MACBETH. To be thus is nothing,
But to be safely thus. (3.1.52–53)

Macbeth's priority up to this point in the play has been "To be thus" —that is, to become king. Now that Macbeth is King, his new priority is "to be safely thus"—to remain king.

Macbeth hasn't forgotten the prophecy that the witches made to Banquo at the same time that they prophesized that Macbeth "shalt be King hereafter!" (1.3.52).

THIRD WITCH. [to Banquo] Thou shalt get kings, though thou be none. (1.3.70)

This prophecy troubles Macbeth to such an extent that he mentions it twice to Banquo in that scene: once almost immediately after the prophecy is made, "Your children shall be kings" (1.3.89), and once again after Ross and Angus tell Macbeth that King Duncan made him Thane of Cawdor, fulfilling one of the prophecies that the witches made to Macbeth.

MACBETH. Do you not hope your children shall be kings,
When those that gave the Thane of Cawdor to me
Promised no less to them? (1.3.127–129)

Macbeth seems more concerned about Banquo's children being kings than with being king himself.

The prophecy isn't mentioned again until the beginning of act 3, scene 1, when Banquo himself raises the issue. Banquo thinks aloud about his suspicions that Macbeth murdered Duncan, "and I fear / Thou play'd most foully for't" (3.1.2–3), and he also notes that the witches said that no descendant of Macbeth will be king, "But that myself should be the root and father / Of many kings" (3.1.5–6).

With Banquo's short speech at the beginning of the act, Shakespeare tells the audience that Macbeth has two reasons to fear Banquo. The first reason is that Banquo suspects that Macbeth murdered Duncan, and the second is that Banquo's descendants, not his own, will succeed him as king. It turns out that Macbeth is much more concerned with Banquo's descendants than with Banquo's suspicions.

Macbeth enters the scene and invites Banquo to his coronation feast, then casually inquires, "Ride you this afternoon?" (3.1.21). A few lines later, Macbeth asks, "Is't far you ride?" (3.1.26).

Macbeth knows that Banquo suspects his involvement in Duncan's death, and he weakly tries to deflect that suspicion by mentioning to Banquo that Duncan's sons, Malcolm and Donalbain, have fled Scotland, "not confessing their cruel parricide" (3.1.34–35). Then Macbeth asks, "Goes Fleance with you?" (3.1.39).

The reason for these incidental questions soon becomes clear. Macbeth engages two murderers to kill Banquo, "and with him... Fleance his son," while they're riding outside the castle.

Until Macbeth can rid himself of Banquo and Fleance, Macbeth wears a "fruitless crown" and carries a "barren sceptre" (3.1.65–66) and will continue to fear the prophecy that Banquo's descendants will be kings.

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Macbeth has heard the witches' prophecies, and since their prophecies about him have all come true, he fears that Banquo's prophecy will also come true. Therefore, Macbeth perceives Banquo and his offspring as threats to his retention of the crown.

Macbeth has ignored Banquo's warning:

...the instruments of darkness tell us truths,
Win us with honest trifles, to betray's
In deepest confidence (1.3.133-135) 

He also has trusted in little things that the witches have predicted, although they have hidden larger and more dangerous changes from him. Macbeth now believes that he can put confidence in the predictions of the witches.
This fatal confidence in the preternatural takes Macbeth into a dimension of the imagination that leads down a bloody and destructive path. In his developing paranoia, Macbeth feels that he must eliminate anyone who prevents his kingship. 

                     ....There is none but he
Whose being I do fear: and under him
My genius is rebuked. (3.1.57-59)   

Because Macbeth perceives Banquo as a threat to his position as king, he sends for his henchmen and gives them the order to kill Banquo and his son Fleance. And so "blood will have blood."

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Macbeth has Banquo murdered because he knows that he is suspicious that Macbeth might have killed Duncan.  He also was told by the witches that Banqo’s sons would be king.  This is the reason why he kills Fleance as well.

Even though Macbeth kills Duncan and takes the throne, he does not feel peace.  He is worried that he will be suspected, and that Banquo knows too much.  Remember, Banquo was there when the witches made their prophecy about Macbeth being king, and they also made their prophecy about Banqo’s sons being king.

Our fears in Banquo

Stick deep, and in his royalty of nature

Reigns that which would be fear'd. (Act 3, Scene 1, enotes etext p. 42).

Macbeth considers Banquo a threat because the witches said his sons would be kings.  This annoys Macbeth, who says “they placed a fruitless crown” upon his head.

Macbeth makes sure the murders know Banquo is their enemy.

So is he mine, and in such bloody distance

That every minute of his being thrusts

Against my near'st of life: (Act 3, Scene 1, p. 44)

Macbeth cannot kill Banquo and Fleance himself, because they are friends and they have friends in common.  So he hires the murders to do it.  After all, to Macbeth“to be thus is nothing/But to be safely thus” (p. 42).  In other words, what is the point of being king unless he is safe from enemies and potential enemies?

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