The ships should take about eight days to reach the first port of call in Portugal
Tens of thousands of people flocked to vantage points in Falmouth to watch the Parade of Sail and the start of the 2008 Tall Ships Race.
More than 20 vessels set off on the race from Falmouth to Portugal, then to Funchal in Madeira, on Saturday.
The three-day event in Falmouth attracted 133,000 visitors, while police said a further 130,000 watched the start of the race.
An estimated 1,000 small boats followed the majestic ships to the start line.
"I've never seen so many boats out on the water," John Hick, one of the regatta organisers told BBC News.
"The car parks are full on the shore and it's a glorious day - what more could we ask for."
Crowds of people gathered to watch the start of the race
Engine trouble on board HMS Cattistock meant the race committee was forced to forego the use of a Royal Navy ship and gun to begin the race. A dock tug and hooter were used instead.
The ships are expected to reach the first port of call in Portugal in about eight days.
Sail Training International said the regatta was the centrepiece of year-long celebrations to mark the 500th anniversary of settlement on the Portuguese island of Madeira.