During a visit to The Light Project in Peterborough, Cambridgeshire, he said because of the coronavirus pandemic it is the time to "do something properly".
The drop-in-centre has helped to house more than 150 people in four hotels during lockdown.
One of them, Robert Smale, 55, who had been living in a tent for six years, said: "I've got no intention of going back on the streets again."
During lockdown, councils in England have been given £3.2m from the government as part of an emergency scheme called Everyone In, to house them, aimed at stopping the spread of the virus.
While talking to rough sleepers, the prince said: "This pandemic has been truly horrendous for everyone - I'm really hoping that the slivers of positivity and the slivers of goodness that might come out of this is in the homelessness side of things.
"You'll never have a better chance nationally to crack homelessness and do something properly."