The Red Devils travel to Eastlands on Monday for a Premier League title showdown with their local rivals.
Going into the game three points clear of their neighbours, United can almost clinch the championship with victory but a win for City will put them above Ferguson's men with two games remaining.
"This is the derby game of all derby games. City are our nearest rivals and it makes everybody step up a notch in terms of anticipation," said Ferguson.
"Whoever loses will be tinged with regret, simply because it's a derby thing. It means everything to the supporters.
"Going in to work next Tuesday morning will be the most important day of their lives, for both sets of fans."
Manchester City won the reverse fixture at Old Trafford 6-1 back in October.