Ferguson retired in May 2013, less than a year after bringing Van Persie to the Premier League giants from rivals Arsenal.
QPR defender Ferdinand, still at United at the time, said the Netherlands international - who struggled for fitness under David Moyes last season and has scored just once this term - was the most affected by Ferguson's departure.
"It took the wind out of everyone's sails. It gave us an extra push to go and win and be successful in that last season," Ferdinand told MUTV.
"Everyone was really appreciative for what he'd done for our careers.
"The person it hit more than anyone was Robin. He'd come the year before, tasted that success and wanted more.
"Visually you could see it hit him harder than anyone else at the time."
United won the 2012-13 Premier League title, with Van Persie scoring a league-best 26 goals.
Though unable to replicate that form since, the 31-year-old did net his first goal of this season in United's 5-3 loss to Leicester City on Sunday.
