Having already lifted the Fifa Club World Cup and the Carling Cup, while an FA Cup semi-final place has been booked at the same time as a seven-point lead has been carved in the Premier League, United have been touted as unstoppable this season.
And Red Devils boss Ferguson - who recorded only a second win in 14 attempts over Inter boss Mourinho - saw his side polish their five-time potential as headers from Nemanja Vidic and Cristiano Ronaldo either side of half-time at Old Trafford boosted dreams of becoming the first team to defend the Champions League title.
With Liverpool and Chelsea booking their place in the last eight on Tuesday, hopes were high that Arsenal and United would ensure all four Premier League teams progressed beyond the first knockout stages of this season's tournament.
But in contrast to United, the Gunners experienced a nerve-wracking night in the Eternal City as Roma's Juan struck to tie the game at 1-1 on aggregate, and then Max Tonetto missed the decisive penalty-kick to send Arsenal through.
Meanwhile, bookmakers' favourites Barcelona eased into the quarter-finals with a 5-2 victory over Lyon at the Camp Nou, and Porto eliminated Atletico Madrid on away goals in Portugal following a 0-0 draw.
If rumours are to be believed, Mourinho harbours aspirations to succeed Ferguson when the Scot decides to call it a day, and the former Chelsea boss, who has made no secret of his fondness for the Premier League, was highly visible before kick-off as he prowled the touchline and tunnel of the defending champions, offering his famous charisma in abundance.
But as the respective United and Inter bosses, who enjoy an amicable relationship, share a vintage glass of post-match claret in the bowels of Old Trafford, Mourinho will hope Wednesday's meeting will not have acted as a possible job interview.
Since famously sprinting down the Old Trafford touchline in 2004 as Costinha's late equaliser sent United crashing out to Mourinho's Porto, who went on to win the competition, the Portuguese had built a record of one defeat in 13 games against Ferguson.
However, Ferguson - who is keen to add a third Champions League winners' medal to his personal collection following 1999 and 2008 successes - banished any suggestions of a 'Mourinho curse' as a 0-0 first-leg draw was followed by a 2-0 victory on home soil.
Mourinho named Patrick Vieira - a man with an equally polished reputation in England following an illustrious spell with Arsenal - in his side, but the decision backfired as early as the fourth minute when the Frenchman inexcusably lost Vidic at a Ryan Giggs corner, allowing the United defender a simple header.
Inter could have drawn level shortly before the half-hour mark, but Sweden striker Zlatan Ibrahimovic failed to replicate Vidic's aerial prowess when nodding a free-kick into the ground and away off the United crossbar.
An agonisingly tense, but extremely absorbing, first half continued in end-to-end style and John O'Shea should have added to United's lead when one-on-one with Julio Cesar, while Ibrahimovic bent an effort just wide of Edwin van der Sar's far post.
Inter came out with purpose in the second half, but in the 49th minute World Player of the Year and Ballon d'Or recipient Ronaldo headed a Wayne Rooney cross past visiting goalkeeper Cesar.
Inter substitute Adriano rattled the United woodwork as the Serie A champions attempted to find a way back into the tie, but the English side held on.
Arsenal were made to work hard in the Olympic Stadium as, after a 1-1 aggregate draw, the Premier League side defeated Roma 7-6 on penalties.
The Gunners visited Rome with a one-goal advantage courtesy of Robin van Persie's penalty in the first leg at Emirates Stadium, with sceptics suggesting that an unbeaten record in Italy, which stretched back to 2002, was under threat.
But throughout the build-up to the match, Gunners boss Arsene Wenger had maintained that it was not in his side's 'culture' to look to shut up shop and sneak through to the quarter-finals.
After stunning European giants AC Milan at the same stage last season, Wenger feels his side has come of age on the continent, but Roma dominated their visitors and the Italian's opener came courtesy of an ugly mix-up between two of the Arsenal's most experienced performers.
William Gallas and Kolo Toure conspired to hamper one and other when attempting to clear Francesco Totti's low cross, offering Juan a simple finish on nine minutes.
Roma, so subdued in the first leg in North London as Arsenal wasted chance after chance, had clearly learnt their lesson and persisted in pressing their opponents in every area of the pitch, preventing trademark pass-and-move football.
Wenger's side were fortunate to not have been punished with a penalty on the stroke of half-time as left-back Gael Clichy appeared to haul down Marco Motta, but Spanish referee Manuel Gonzalez remained uninterested.
Arsenal seemed more intent after the half-time break, but Doni in the Roma goal was not truly tested as Wenger, who decided to introduce Theo Walcott, was happy to see former player Julio Baptista horribly miscue with the goal gaping in the best chance of the 90 minutes.
After a goalless period of extra-time, penalties were required. Eduardo and Vucinic failed from the spot, and then Tonetto blazed over the bar to send Arsenal through.
Barcelona continued to live up to their billing as the side most likely to sample success in Rome on 27th May as they brushed aside Lyon 5-2 to wrap up a 6-3 aggregate win.
Thierry Henry set Pep Guardiola's side on their way in the Camp Nou in the 25th minute as he collected Rafael Marquez's pass to stride into acres of space and slot past Hugo Lloris.
And with Lyon, who had been forced back from the opening whistle, still staggering, Barca doubled their lead as Henry, who had netted in the 1-1 first-leg draw, scored his third of the tie two minutes later.
Guardiola's men - who have reached their 34th Copa del Rey final since the opening meeting in France two weeks ago - were on song and deservedly had their third on 40 minutes as Argentina star Lionel Messi jinked in from the right touchline, beating five Lyon defenders, before converting in stunning style.
And there was still time before the half-time interval for Samuel Eto'o - who has enjoyed a rejuvenated season and is the current top scorer in the Primera Liga - to make it 4-0, while Lyon pulled back some pride as Jean Makoun headed in at a 44th minute corner.
Lyon halved the deficit with the first attack of the second half as Brazilian Juninho - who netted a trademark free-kick in the first leg to earn praise from Guardiola - rolled in for a slightly less spectacular goal.
But any hopes of a dramatic comeback were erased as Juninho was dismissed for dissent and a second booking on the stroke of full-time, while Seydou Keita netted Barca's fifth on the night in injury-time.
Porto and Atletico Madrid played out a goalless stalemate in Portugal, allowing the home side to progress on away goals following a 2-2 draw in the first leg.
A tense night at the Estadio Dragao saw a game of few chances. Fernando had an effort for Porto in the first half, while Sergio Aguero turned down the opportunity to pass as Atletico's best attack went to waste.
The Spanish side introduced Diego Forlan in the second half after the striker had surprisingly been left on the bench, but it was Porto who almost snatched the win on the night as Lisandro hit a post in the dying minutes.