Having kicked off Group H with a 2-1 win in the French capital and 5-0 shellacking of RB Leipzig, Ole Gunnar Solskjaer’s side knew they would go through to the round of 16 if they avoided defeat on Wednesday.
United looked well placed to secure that vital point after Marcus Rashford cancelled out Neymar’s early stunner, but Marquinhos and Neymar goals either side of Fred’s belated sending off saw PSG run out 3-1 victors at Old Trafford.
The result means the top three in Group H are all level on nine points heading into the final fixtures, with the Red Devils knowing a point in Leipzig will see them reach the last 16.
Neymar completed a win he started in style in the sixth minute, with PSG on top during an opening that saw Fred somehow avoid a red card after pushing his head into Leandro Paredes’ midway through the first half.
Referee Daniele Orsato only gave a yellow card despite reviewing the decision on the monitor and Rashford soon levelled with an effort that deflected in off Danilo.
Fred was perhaps fortunate to avoid a second yellow card before the break, which United returned from strongly as Martial twice wasted fine chances – the second effort after an outrageous Edinson Cavani chip that hit the bar.
But PSG would seal a much-needed win as Marquinhos turned home from close-range before Fred finally received his marching orders, albeit on this occasion he could count himself unlucky.
Neymar added a third in stoppage time after United failed in their search for another equaliser.
The Brazil star showed flashes of brilliance on Wednesday, including the early opener at the end of a fine team move.
Having stripped Rashford of possession near their own goal, Thomas Tuchel’s men went on a break that ended with Neymar firing home from an acute angle after reacting superbly to a blocked Kylian Mbappe strike.
David De Gea will have been annoyed not to have kept out the effort but was able to thwart PSG’s next attempt when Alessandro Florenzi took aim, before Neymar tried an acrobatic effort.
United’s meek response to that early setback looked set to be compounded by a red card when Paredes fell to the deck clutching his face after Fred pushed his head into his.
The VAR informed referee Orsato to check the monitor but the referee only showed a yellow card after watching the replay – a let-off that jolted United into life.
Martial saw his effort saved by Keylor Navas and Aaron Wan-Bissaka cut the parried ball back to Rashford, whose low strike cannoned off Danilo and flew into the PSG goal.
United were now controlling possession but Fred was still riding his luck, having stepped on Paredes’ foot in a challenge that led to the PSG midfielder being booked.
The hosts returned well from the break and Martial was guilty of ballooning an effort into the Stretford End after being found by Rashford, having linked up superbly with Cavani.
PSG’s all-time top scorer and Fred had attempts as United continued in the ascendancy, with Cavani going close to scoring an outrageous goal in the 57th minute.
The veteran raced through and tried an exquisite chipped effort that left Navas stranded and came back off the bar. Bruno Fernandes cut the loose back to Martial but the strike was blocked.
Mbappe and Neymar continued to prove a handful, with the latter passing for Florenzi to send over a cross that Marquinhos met with a header that clipped the crossbar.
De Gea tipped a low effort from Mitchel Bakker around the post and fellow substitute Ander Herrera made an impact from the resulting corner, with the former United midfielder hitting a wayward strike that Abdou Diallo turned across for Marquinhos to steer home.
Matters soon worsened as Fred finally got the red card he had been threatening to collect all night, although he appeared to get the ball in the challenge that finally brought his marching orders.
Substitute Paul Pogba went close with an outstanding strike and Fernandes’ near post header was saved as depleted United pushed, only to be caught cold at the end as Rafinha cut back for Neymar to turn home in stoppage time.