Liverpool won two and drew one of their opening matches without conceding a goal, but that run ended when West Ham won at Anfield for the first time since 1963.
Rodgers believes making the short trip to United can help his players quickly put that defeat behind them.
"Winning a game like this can give you psychological boost," he told reporters on Friday.
"United is a huge club and will always be under scrutiny. The intensity of this fixture is still there. The players will feel it.
"We've had two tough games away from home and performed well in terms of our organisation. We also want to be really creative.
"This is the biggest derby game in the history of this league. Winning a game like this can give you psychological boost."
Although Liverpool's nearest geographical neighbours are Everton and United are closer to Manchester City, the intensity of the rivalry between United and Liverpool down the decades overshadows both those more local conflicts.
Liverpool established the record number of English championships when they won their 18th in 1990.
Former United manager Alex Ferguson vowed to "knock Liverpool off their perch" after taking over at Old Trafford in 1986 and by the time he retired two years ago he had done just that, leading United to 13 titles to take their total to a record 20.
Sky Sports has been highlighting the greats from both club's pasts in their advertising trailers for the match which is being broadcast live on Saturday at 1630 GMT, but of more concern to Rodgers was the improving fitness of his striker Daniel Sturridge who has not played since April.
Sturridge will not be ready to face but Rodgers said Adam Lallana and Jordan Henderson, who have both missed the last two matches with injuries, will be assessed before the game.
"Daniel has looked really sharp in training, the best he has looked fitness-wise in 18 months," he said.
Liverpool will be without Philippe Coutinho at Old Trafford because the creative Brazilian midfielder is suspended after being red-carded against West Ham.
(Reporting by Mike Collett, editing by Ed Osmond)
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