Ferguson has become a coaching icon since taking over United, but one of his former players, Sunderland boss Steve Bruce, will be out to ruin the day.
The Black Cats have lost only once in their last four games, and striker Nicklas Bendtner believes his side will be up for the occasion.
"Whenever you play Manchester United it is always a big game," Bendtner said.
"It is something we are looking forward to and although the game will be very difficult for us, we will be doing our best to get something out of it.
"Anything can happen in football and we will go there with a positive attitude."
United would not only like to collect three points from the match on Ferguson's big day, but the club needs to begin to try and chip away at Manchester City's five-point lead atop the table.
The Red Devils bounced back from a humiliating 6-1 home defeat against City last weekend by securing a 1-0 win at Everton, and United will hope to keep the pressure on the Citizens with three more points.
One United player who knows Sunderland well is striker Danny Welbeck, who spent last season on loan at the Stadium of Light.
Welbeck performed well for Bruce and his team and gained valuable experience with the club, but he has promised those feelings will be put aside on Saturday.
"I know quite a few of the players, so it'll be good to see them again, but, when it comes down to it, I'll be ruthless," Welbeck said. "I just want to win the game. There's no friends out on the pitch."
City will attempt to keep its lead at the top by securing a win at Loftus Road against QPR, with Newcastle entering the weekend in third place and looking to maintain its unbeaten record with a good result at home against Everton.
Chelsea has lost its last two matches and travels to Blackburn, Arsenal owns four wins from its last five games and hosts West Bromwich, while Aston Villa tries to get back on track against Norwich City after earning one point from three games.
Liverpool brings a five-game unbeaten streak into its match with Swansea City at Anfield, Wolverhampton and Wigan square off at Molineux with the Latics on a seven-game losing streak and Stoke City travels to Bolton with Wanderers having lost eight of their last nine games.