The Argentine is set to coach his remaining games with the USA in the current international break before officially starting at Old Trafford on Wednesday, November 18th.
Pochettino has been courted by United in the past, but will now succeed former coach Michael Carrick and look to guide the club out of the Premier League's relegation zone.
"The club has reached an agreement with the U.S. Soccer Federation for Mauricio and his staff to be released after the conclusion of their responsibilities with the U.S. Men’s National Team," Manchester United said in a statement.
"The Argentinian is renowned for his high-intensity, attacking style of football, his dedication to building strong, cohesive teams and his outstanding record of developing individual players."
The 54-year-old is best known in England for managerial stints at Southampton, Tottenham and Chelsea, while he also took charge of PSG and the USA national team.
Some of his greatest success came with Spurs, where he formed a formidable side featuring the likes of Harry Kane, Heung-Min Son, Christian Eriksen and Dele Alli - taking them all the way to the Champions League final in 2019.
Pochettino also oversaw huge growth earlier in his career at Southampton, with his side finishing eighth in 2014 and recording what was then their highest-ever Premier League points tally.
More recently, the Argentine managed Ligue 1 giants PSG, winning both the league and Coupe de France during his 18-month tenure, before moving on to coach Chelsea and then the USMNT.
Pochettino's first game in charge of Manchester United will come against Liverpool at Anfield on Sunday, November 22nd.
