While the old rivalry cannot be accurately described as the top-of-the-table tussle it once was, United in particular know that only a win will do if they are to stay in touch with the chasing pack.
This is the first of three fixtures in a frenetic week for these squads, including a return to Europa League action on Thursday and Premier League matches on Sunday.
These are bleak times in the league for United, who have one win in five matches and produced a limp 2-0 defeat at West Ham United in their last outing.
The result did not flatter West Ham and United's misery was compounded by an inept display of finishing and the premature departure of Marcus Rashford with a groin strain.
A 1-0 home win over Leicester City is United's only victory since then, failing to score more than once in any of their matches.
With trips to AZ Alkmaar and Newcastle United coming up before the international break, United will be anxious to extend their run of home wins to four matches.
That win over Leicester seemed to have set them back on track following their shock defeat to Crystal Palace in their second home match of the season.
Matters worsened further when United scraped through to the next round of the EFL Cup on Wednesday night, edging past Rochdale after the League One strugglers had equalised at Old Trafford to force penalties following a 1-1 draw.
Recent form: WDLDWL
Recent form (all competitions): LDWWWD
While United were putting in a stultifying showing at the London Stadium, Arsenal almost fell to a much more surprising defeat across the capital.
Only two goals in the final nine minutes of normal time rescued the Gunners after newly-promoted Aston Villa twice took the lead at the Emirates Stadium.
The joint-winner of last season's Golden Boot also struck late in a much more assured performance at Eintracht Frankfurt the previous Thursday.
Arsenal made an excellent start to their Europa League season, beating last season's semi-finalists 3-0 to go joint-top of their group.
With the visits of Standard Liege and Bournemouth to come on Thursday and Sunday, Arsenal will fancy themselves to have a perfect week should they win at Old Trafford.
Unai Emery's side are on a reasonable run of away form, winning four of their last six trips, with their only defeat coming at runaway Premier League leaders Liverpool.
Their midweek home EFL Cup tie could hardly have gone better, cruising to a 5-0 victory over Championship high-fliers Nottingham Forest with the help of impressive performances from several young prospects.
Recent form: WWLDDW
Recent form (all competitions): LDDWWW
Rashford is still expected to be absent for United, having limped out of the defeat against West Ham with a second-half groin problem.
Midfielder Paul Pogba, who sustained an ankle injury before the international break, returned against Rochdale but still struggled with the problem, while Anthony Martial is a major doubt and Luke Shaw is still out.
Ivorian defender Eric Bailly is expected to be out until November, having returned to light training after suffering a knee injury in pre-season.
Versatile young livewire Timothy Fosu-Mensah is United's other long-term absentee, as the Dutchman is still returning from surgery on ligament damage sustained while on loan at Fulham last season.
Hector Bellerin returned from a long-term Achilles tendon injury by playing the final 13 minutes against Forest, giving Emery another option at full-back.
Defender Kieran Tierney, signed from Celtic for £25m during the summer, is likely to make his first Premier League start after debuting against Forest.
Attacking midfielder Emile Smith Rowe was substituted just before the interval on Tuesday as a precaution following a collision, so is unlikely to be available for the next week or so.
Manchester United possible starting lineup:
De Gea; Wan-Bissaka, Lindelof, Maguire, Young; McTominay, Matic, Pogba; James, Mata, Greenwood
Arsenalpossible starting lineup:
Leno; Maitland-Niles, Sokratis, Luiz, Kolasinac; Willock, Guendouzi, Ceballos; Saka, Pepe, Aubameyang
Head To Head
From Ryan Giggs whipping his top off following a dazzling extra-time winner in the FA Cup semi-final in 1999 to Martin Keown taunting Ruud van Nistelrooy during the goalless Battle of Old Trafford in 2003, this is a pairing that instantly brings to mind memorable matches.
There was the 2001-02 season, when Premier League winners Arsenal beat United three times over the course of the season with an 8-2 aggregate scoreline, and the contrasting humiliation of August 2011, when United won 8-2 in a single disastrous 90 minutes for Arsenal at Old Trafford.
United have not lost to Arsenal at home since September 2006, when Emmanuel Adebayor's 86th-minute winner gave the visitors their last victory there.
The Red Devils have the overall lead in the head-to-head. There have been 48 draws and 83 Arsenal wins, but United can register their 100th victory over Arsenal should they win here.
We say: Manchester United 1-1 Arsenal
In a season when every loss to sides outside the top two will raise questions around the durability of these squads, the likelihood is that Solskjaer and Emery will be happy to avoid defeat.
The less certain names on the teamsheets could dictate which way the contest between these contenders goes. The likes of Pogba, Rashford and Martial are sometimes at their best on the most intense occasions for United.