The Red Devils are in the process of piecing together a Premier League title bid, but they have slipped five points adrift of arch-rivals Manchester City.
With Pep Guardiola’s free-scoring outfit sweeping aside all before them, the chasing pack cannot afford any slip-ups.
Taking that into account, former United star Neville believes Mourinho must break from tradition on the road and send his team out with an attacking mindset at Stamford Bridge on Sunday.
He told Sky Sports, having seen the Red Devils grind out a 0-0 draw at Liverpool in their last trip to a fellow title hopeful: “Manchester United's trip to Chelsea on is a huge game for the Premier League title race.
“We saw what Manchester City did to Chelsea, beating them 1-0 and probably producing one of the best performances we've seen in three or four seasons.
“United have to win the game. I don't think a draw is good enough but I think they are ready to win a game of this magnitude.
“Chelsea have the players to hurt you with Eden Hazard coming back to form. Will Jose look to man-mark him with Ander Herrera? Tactically I think it will be another game where he comes up with a plan to win the game.”
While Mourinho will be back in familiar surroundings this weekend, so too will former Chelsea striker Romelu Lukaku.
The Belgium international has seen a bright start to his time with United – which delivered 11 goals in 10 games – make way for a five-match run without finding the target, but Neville believes that recent criticism of a man branded “untouchable” by Mourinho is unfair.
He added: “I think Romelu Lukaku probably dipped in the previous three games, which happens when you join a new side, but he was better against Tottenham and started bullying their defenders.
“Forget the chances he's missed, if he keeps performing like that he will score goals in the big games and he looked razor sharp.
“There's not actually that many strikers who score lots of goals in the big games so I think it is a harsh criticism, but if United are to get a result at Chelsea they need another big performance from him.”
Prior to heading to west London, United have a Champions League home date with Benfica to contend with on Tuesday.