The US rocker - who was joined by his E Street Band - played hits such as Badlands, Born In The USA and Born To Run, before ending with a cover of Twist And Shout, the song made famous by The Beatles.
The 62-year-old's set topped the bill at the festival, which had previously seen performances from Noel Gallagher's High Flying Birds, Zulu Winter, The Vaccines and Spector.
The promoter of the Isle of Wight festival apologised for the chaos caused by heavy rain at the event.
But John Giddings said that he had been amazed by the resilience of the 55,000-strong crowd which overcame the mud to enjoy the concerts.
He said: "I am really sorry to everyone who had problems as they arrived at the festival but I hope that I have made up for it by providing one of the best weekends of music ever."
The festival was affected by a deluge which saw gridlocked drivers forced to sleep in their cars as the car parks at Seaclose Park, Newport, had become flooded and inaccessible because of the mud.
The queues caused ferry companies to suspend their services and about 600 people were stranded on ferries on the Solent as the cars could not disembark because of backed-up traffic on the island.