Bruce enjoyed huge success as a player and captain at United but since moving to the dugout he has come to associate the club with disappointment.
He came closest to beating Ferguson in 2009 when his Sunderland side were denied a 2-1 win by Anton Ferdinand's last gasp own-goal and lost the chance for good when his former mentor retired at the end of last term.
A win over the Red Devils would still represent a huge scalp, with Bruce rating them as title challengers despite losing five times in 17 under Ferguson's successor David Moyes.
"I've never beaten them and I don't know if this is a better chance. Just because they've changed manager doesn't mean that mentality's going to go away," said Bruce.
"It's ingrained in them. For a lot of the players, they're used to success. They know how to win a league. You can never write them off because they are capable of going to win eight, nine or 10 games on the spin.
"Usually, they get stronger in the second half of the season. That's always been the case with them, so I wouldn't write them off.
"I don't think the aura has gone. In my experience, whether you're Bayern Munich or Scunthorpe, with Manchester United it's a big occasion.
"The ring of Manchester United just seems to have a special pull about it. It's true you either love them or hate them but you can't argue it's a magical draw when you play against them, always."
Whether or not United do mount a credible defence of their Barclays Premier League title - and, with the likes of Liverpool, Arsenal and Everton performing ahead of expectations to join Chelsea and Manchester City in the race, they clearly have work to do - Bruce has no worries about Moyes' position.
The United board gave the former Everton boss a six-year contract as a show of faith in his ability and Bruce believes he will be given all the time he needs to piece together his own side.
"I don't think they would contemplate it (sacking Moyes after a season)," he added.
"What is needed is for David to be given the chance and this is where Manchester United stand alone. They'll be patient, they believe they've got the right man for the job and they'll give him time to make his own stamp on the club.
"When you're following in the footsteps of Sir Alex, whoever you are, it's a difficult job to grasp. David has handled himself fantastically well in a dignified manner, like we knew he would.
"He found it a little bit difficult to start with, but the signs are that they're starting to get into gear."