This will be the Oxfordshire-born official's third game involving the Magpies this term after taking charge of their Emirates FA Cup third round replay win against Rochdale, with the 51-year-old booking United's Tom Allan, who made his professional debut that night, during the 4-1 triumph at St. James' Park.
Scott was also the man in the middle for Newcastle's 1-1 draw at home to Watford back in August, dishing out five yellow cards that day, booking Paul Dummett and Isaac Hayden.
Promoted to the Select Group of Referees in 2015, Scott has refereed 21 games so far this season across the Premier League, Championship, FA Cup and Carabao Cup, handing out 65 yellow cards and five reds in total.
On Saturday at St. Mary's Stadium, Scott will be assisted by Neil Davies and Richard West while Andy Woolmer will be the fourth official. Peter Bankes will be the video assistant referee and will be aided by Andy Garratt.