However, Newcastle themselves have put together three straight wins to climb away from trouble and will be hoping to capitalise on their opponents' poor away record.
The Magpies have lost just once since January to climb into the top half of the table, 10 points clear of the relegation zone and just two short of the magic 40 mark.
A fourth successive league victory would be the first time that Newcastle have managed such a feat since reeling off five in a row under Alan Pardew in the autumn of 2014.
Jonjo Shelvey has been one of the inspirations behind Newcastle's upturn in form and the midfielder finally scored his first goal of the season in last weekend's 2-1 triumph over Leicester City - the Tyneside club's first away win since New Year's Day.
England are not blessed with options in the centre of the park, so Shelvey will hope to catch Gareth Southgate's eye over the remainder of the campaign and get an opportunity to stake his claim for World Cup selection.
The 19 points that Newcastle have accumulated since the start of 2018 is only bettered by the current top four, although United have struggled to compete with the elite in head-to-head competition.
Benitez's side have lost seven of their nine league games this season against the big six, with the only victory coming at home to Manchester United in February. There is still time for another notable scalp, with Chelsea and Tottenham Hotspur on the horizon after Arsenal's visit to St James' Park.
Recent form: WDLWWW
The Gunners nearly slipped to an embarrassing loss at CSKA Moscow on Thursday, but late goals from Aaron Ramsey and Danny Welbeck earned them a 2-2 draw which secured a comfortable 6-3 aggregate victory.
To save their season, with a 13-point deficit still separating them and rivals Tottenham Hotspur in fourth, Arsenal must now go through favourites Atletico Madrid in the last four to reach the Europa League final.
Although domestic matters have taken a back seat to Arsenal's pursuit of continental glory, the Londoners have actually strung together a run of three consecutive wins, after a horror run of four defeats in five games.
Pierre Emerick-Aubameyang, cup tied in Europe, has provided Arsenal's league campaign with some fresh impetus, scoring five goals in four starts. The January signing from Borussia Dortmund is already up to six league goals, which makes him four short of Arsenal's top scorer for the top-flight campaign - Alexandre Lacazette.
Welbeck is also in a rich vein of form with five goals in as many matches and will certainly be on Southgate's radar, but Jack Wilshere's latest injury might raise more doubts over his place on the plane to Russia this summer.
Arsenal are the only Premier League team yet to pick up a point on the road in 2018, losing all four of their away top-flight matches since the turn of the year. They have not lost five successive away league games since 1984, and last started a calendar year with five straight away league defeats in 1925.
The Gunners' total of three away league wins all season is less than Watford, Newcastle and Burnley, and the Clarets could climb above Arsenal into sixth this week if Arsene Wenger's side suffer more misery on their travels.
Recent Premier League form: LLLWWW
Recent form (all competitions): WWWWWD
Benitez has a fully-fit squad to choose from and could name an unchanged lineup from the one that started at the King Power Stadium, although Islam Slimani is available for the first time since joining on loan from Leicester after recovering from injury.
Wenger is likely to rotate again but may not make as many changes as he did for the 3-2 win over Southampton as the first leg against Atletico is not until April 26.
Wilshere and Aaron Ramsey are both carrying niggles so Mohamed Elneny may start, having had his red card against the Saints overturned. Granit Xhaka may also be recalled after missing the trip to Moscow through illness.
Newcastle possible starting lineup:
Dubravka; Yedlin, Lejeune, Lascelles, Dummett; Ritchie, Diame, Shelvey, Kenedy; Perez, Gayle
Arsenal possible starting lineup:
Cech; Bellerin, Koscielny, Mustafi, Kolasinac; Elneny, Xhaka; Iwobi, Ozil, Welbeck; Aubameyang
Head To Head
Arsenal have won all of their last 10 league games against Newcastle, although the last three have all been by a narrow 1-0 scoreline including in December when Mesut Ozil's goal settled things at the Emirates Stadium.
United's most recent home victory over the Gunners came back in 2005 courtesy of a Nolberto Solano winner, but they do have fond memories of coming from four goals down to draw with Arsenal back in 2011, with the long-range equaliser coming from the late Cheick Tiote.
We say: Newcastle 1-1 Arsenal
This might be the opportune moment for Newcastle to end their losing streak against the Gunners, who could suffer from a Europa League hangover after a trip to Russia and back. They have been flimsy on the road anyway, without the excuse of extra miles in their legs.
St James' will be rocking because of Newcastle's recent form - three home league wins on the bounce without conceding - but Arsenal's forwards are really enjoying themselves of late and that should be enough to ensure that the Londoners leave Tyneside with at least a point.