The closure will come two days after Pope Benedict XVI's arrival in Sydney for World Youth Day.
Up to 180,000 pilgrims are expected to make the nine kilometre journey from North Sydney, across the Sydney Harbour Bridge, through Darling Harbour and on to Randwick Racecourse in the city's east.
"This event will be the second largest event in Sydney, dwarfed only by the Olympics," Mr Roozendaal said.
"It will present major traffic challenges."
Mr Roozendaal would not confirm if the entire route would be closed for the journey.
"There will have to be road closures, but we will be giving the community plenty of information and updates so they can plan for the challenges that can be brought with this program," he said.
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