Poole, 19, moved to Old Trafford in 2015 from Newport County, where he played under current Cobblers boss Justin Edinburgh.
But his only United appearance to date was as a late substitute in the Europa League in February 2016.
The Wales Under-21 international comes in as competition for centre-backs Ash Taylor and Leon Barnett.
Edinburgh said: "He is a central defender who is comfortable on the ball. He is strong, he leaps well and he has all the attributes to be a top, top player.
"He is mobile and he will complement the other defenders we have at the club well."
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League One side Northampton Town have signed young Manchester United defender Regan Poole on a season-long loan.