Mourinho admits Manchester United are in "big trouble" because of a crippling injury list made worse by the knee injuries suffered by Ibrahimovic and Marcos Rojo in the Europa League win over Anderlecht.
Rooney, an unused substitute for that game, has played just 86 minutes of football since the beginning of February and he is widely expected to leave Old Trafford this summer in a bid to play on a more regular basis.
But with Ibrahimovic likely to be sidelined possibly for the rest of the season, Mourinho feels now is the time for Rooney to step up for a final hurrah United, despite the loss of form and the toll injuries have taken on him.
Zlatan Ibrahimovic picked up a nasty looking injury against Anderlecht Zlatan Ibrahimovic suffers worrying knee injury against Anderlecht Fri, April 21, 2017
Zlatan Ibrahimovic suffered a worrying knee injury during Manchester United's win over Anderlecht
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Ibrahimovic appeared to hyperextend his right knee
Rooney, 31, has become a peripheral figure at Old Trafford and has started only 19 out of the 54 games United have played in all competitions this season.
Mourinho insists however he can still play a key role for United in their twin bids to reach the Champions League because he is such a strong character.
"He has a good mentality, he's a fighter," said the United boss. "He's a strong man, even if he's not in the best condition, even if he's not in the level of sharpness that you need to play high-level football, but he has the experience and character, so he has to.
"Now we need absolutely everyone. Now I even have to think that Axel Tuanzebe, who has to go to the under 'something' World Cup in Korea, because maybe Axel has to come now because now we need everyone."
Jose Mourinho has called on Wayne Rooney to fill Zlatan Ibrahimovic's void
Mourinho says United are in desperate shape going into tomorrow's testing trip to home-specialists Burnley.
Rojo's knee injury has left Mourinho with just Eric Bailly as his only recognised fit centre-half.
"We're in trouble," he said. "In this moment, Eric Bailly has played six matches in a row and we have lost Rojo.
"We don't have Jones or Smalling, so we are in trouble and now we lose Zlatan too. But in attack, we have options and Rooney is coming, and let's see if Juan Mata can also return before the end of the season. Let's see what happens."
Mourinho will bring back Ander Herrera and Ashley Young to face Burnley tomorrow before displaying some black humour by quipping: "That's it. There's no-one else to play!"
Marcus Rashford was on target last night to secure Manchester United's place in the last four
A big plus for United is Marcus Rashford's return to goalscoring form and the 19-year-old England striker netted the extra-time winner against Anderlecht to take his tally to three in his last four goals and 10 in total.
Mourinho has big hopes for Rashford and claims it would make "no sense" for England to take him to the Under-21 European Championships in Poland in June.
He thinks Rashford has already proved he belongs with Gareth Southgate's senior squad.
"I don't want to go in that direction," said Mourinho. "I just feel that when a player reaches a certain level, it doesn't make a lot of sense to drop levels.
"It's like now I'm going to play him in the Under-23s to win, let's say, a derby against Man City? Would I do that? No.
"Nicky Butt doesn't pick him to play that game, although he could because of his age.
"I think when you reach a certain level, and you reach that level for a long time, I don't think it makes sense, but the power is in their hands."