The 2018/19 fixtures were released on Thursday morning and Rafa Benítez's side will entertain Tottenham Hotspur on Saturday, August 11th (subject to change).
United haven't won on the opening day of a season since 2012/13, when Spurs were also the visitors to St. James' Park.
That day, Demba Ba opened the scoring but Jermain Defoe equalised for the North London side - only for Hatem Ben Arfa to score from the spot with ten minutes left to give the Magpies all three points.
In the following two seasons, Manchester City recorded two victories over United in successive curtain-raisers, triumphing 4-0 at the Etihad Stadium in August 2013 before running out 2-0 winners at St. James' Park a year later.
Steve McClaren's first game in charge of Newcastle, on the opening day of the 2015/16 campaign, was a 2-2 home draw against Southampton while last season, ten-man Newcastle were beaten 2-0 by Spurs on Tyneside.
But of course, the first game does not define a season - in 2016/17, the Magpies lost 1-0 at Fulham before going on to lift the Sky Bet Championship title.
And in 1926/27, United lost two of their first three matches - but ended up as league champions.
United's first ever Premier League game was also against Spurs, on 14th August 1993. Kevin Keegan's side were beaten 1-0 but finished third that term.
You can see Newcastle's full 2018/19 Premier League fixture list here.