The Red Devils came from behind to hold their French counterparts to a 1-1 draw in Leigh last week, but a 3-1 beating at the Parc des Princes in the second leg condemned them to a premature continental exit.
Marc Skinner's side fell behind with just 17 minutes on the clock in the French capital, as Dutch striker Lieke Martens lashed home the opening goal after Tabitha Chawinga was thwarted by the feet of Mary Earps.
Within just two minutes of the second half, Lisa Naalsund opened her account for Man United to get the visitors on level terms, but Martens was on hand to restore PSG's advantage straight away, as Chawinga burst to the byline and cut back for her teammate to finish from close range at the near post.
The die was cast for Skinner's team in the 57th minute, as Sandy Baltimore easily beat Hannah Blundell for pace on the right flank and remarkably chipped the ball over Earps from a tight angle.
A disallowed Leah Galton goal for a perceived push on Clare Hunt rubbed salt into the wounds for the Red Devils, whose defeat means that Chelsea will be the only English team in the tournament proper.
The group-stage draw for the Women's Champions League takes place on Friday, while Man United will aim to bounce back on Sunday, when they travel to Everton for a Women's Super League fixture.
Heart Of Midlothian 
Celtic 
Reims 
Lyon 
PSV 
Groningen 
Celta Vigo 
Barcelona 
Benfica 
Estrela Da Amadora 
Sparta Rotterdam 
AZ Alkmaar 
Southampton 
Liverpool 
Como 
Fiorentina 
Sevilla 
Rayo Vallecano 
Ajax 
Pec Zwolle 
Palermo 
Sampdoria 
Ipswich 
Manchester Utd 
Napoli 
Roma 
Moreirense 
FC Porto 
Leganes 
Real Madrid 
Lazio 
Bologna 
Empoli 
Udinese 
CSKA Moscow 
Rubin 
Slovan Bratislava 
AC Milan 
Sparta Praha 
Atletico Madrid 
Valencia 
Stade Brestois 29 
Bayer Leverkusen 
Red Bull Salzburg 
Bayern Munich 
Paris Saint Germain 
Inter 
RB Leipzig 
Manchester City 
Feyenoord 
Sporting CP 
Arsenal 
FC Rostov 
Spartak Moscow 
Aston Villa 
Juventus 
Club Brugge