He took charge of United's 2-2 draw with Southampton in August, booking six players - including Jamaal Lascelles and Fabian Schär - and awarding a stoppage-time penalty to the Saints, which was converted by James Ward-Prowse.
The Wigan-born official is now in his seventh season in the top flight, having worked his way up through the lower leagues prior to making a first outing in the middle of a Premier League fixture back in August 2014.
He had previously been named among the National Group of Referees in 2009, a year after being an assistant referee during the Magpies' league defeat to Hull City at St. James' Park.
Tierney has also taken charge of a Championship play-off final at Wembley - Aston Villa's win over Derby County in 2019 - and a handful of significant fixtures lower down the pyramid, though in the last few years he has become an established Premier League official, having been named on FIFA's list of referees in January 2018.
Last season, he took charge of three United games - the 0-0 draw with Liverpool, a 3-1 defeat at Manchester United and March's 1-1 draw with Aston Villa. In total, he refereed 26 games across the Premier League, Championship, FA Cup and Carabao Cup, showing 95 yellow cards and three red.
This term, he has shown 30 yellow cards in nine matches - including the Community Shield clash between Leicester City and Manchester City and a World Cup qualifier between Moldova and Austria - but has yet to send a player off during the current campaign.
On Saturday, Tierney will be assisted by Constantine Hatzidakis and Neil Davies. Martin Atkinson will be the fourth official while at Stockley Park, David Coote will be the Video Assistant Referee, assisted by Nick Hopton.