What was Big Willy Shakes going for?
You've probably figured out from Margaret's little speech that she's being serious. She wants York's head chopped off. And that's exactly what happens next.
The speech doesn't tell us, though, that Shakespeare is the first to use this phrase. He used it again in the next play in this history series, Richard III. Richard may hate Margaret with a passion, but hey, that doesn't mean he can't learn from her.
He orders "off with his head!" when he suspects a traitor is in his court (3.4.77). What goes around comes around, we guess—even if it's heads rolling.