The Red Devils were held to a frustrating 1-1 draw with FC Twente on matchday one and have since suffered a humbling 3-0 defeat to Tottenham Hotspur in the Premier League at Old Trafford, piling more pressure on manager Erik ten Hag.
As for Porto, they lost 3-2 away against Bodo/Glimt in their Europa League opener, but bounced back in emphatic fashion by thrashing Arouca 4-0 on home soil in the Primeira Liga on Sunday.
Here, Sports Mole takes an in-depth look at the head-to-head record and previous meetings between the two sides.
Head-to-head record
Previous meetings: 8
Porto wins: 2
Draws: 3
Man Utd wins: 3
Porto and Man United have faced each other a total of eight times in European competition, with the Red Devils edging the head-to-head record with three wins to the Dragons' two, while there have also been three draws.
The first time these two teams locked horns was back in 1977 in the second round of the European Cup Winners' Cup. Porto cruised to a 4-0 home victory in the first leg before Man United fought back in the reverse fixture at Old Trafford to win the second leg 5-2, but the Red Devils ultimately lost the thrilling contest 6-5 on aggregate.
The next six encounters between Porto and Man United were all in the Champions League, including a 4-0 aggregate victory for Sir Alex Ferguson's Red Devils in the quarter-finals (a 4-0 first-leg home win followed by a 0-0 draw in the second leg).
Porto got their revenge in 2004, though, following up a 2-1 last-16 first-leg win at the Estadio do Dragao - courtesy of two goals from Benni McCarthy - with a hard-fought 1-1 draw at Old Trafford in the second leg.
Paul Scholes's opener was cancelled out by a dramatic 90th-minute equaliser from Costinha to seal a 3-2 aggregate win, and Jose Mourinho's side went on to win the Champions League for the second time in their history.
Man United then triumphed in Europe's most prestigious club competition in 2008, and the following season squared off with Porto in the quarter-finals, prevailing 3-2 on aggregate after drawing the first leg 2-2 at Old Trafford and winning the reverse future 1-0 in Portugal, thanks to an iconic 40-yard strike from Cristiano Ronaldo.
Thursday's contest between Porto and Man United will represent the first time that these two teams have butted heads in the Europa League.
Previous meetings
Apr 15, 2009: Porto 0-1 Man United (Champions League Quarter-Final Second Leg)
Apr 7, 2009: Man United 2-2 Porto (Champions League Quarter-Final First Leg)
Mar 9, 2004: Man United 1-1 Porto (Champions League Last 16 Second Leg)
Feb 25, 2004: Porto 2-1 Man United (Champions League Last 16 First Leg)
Mar 19, 1997: Porto 0-0 Man United (Champions League Quarter-Final Second Leg)
Mar 5, 1997: Man United 4-0 Porto (Champions League Quarter-Final First Leg)
Nov 2, 1977: Man United 5-2 Porto (Cup Winners' Cup Second Round Second Leg)
Oct 19, 1977: Porto 4-0 Man United (Cup Winners' Cup Second Round First Leg)
Read more on Porto vs Manchester United
Mount, Maguire latest: Man United injury, suspension news vs. Porto
Click here to read our full preview for Porto vs Manchester United
Ten Hag to make three changes? Predicted Man United lineup vs. Porto