Known as Little Red, the new service begins with a Manchester to Heathrow flight, kicking off a four-times-a-day service between the two airports.
Next Friday a six-daily Heathrow-Edinburgh service begins, followed by thrice-daily Heathrow-Aberdeen flights from April 9.
Virgin is starting domestic services after take-off and landing slots at Heathrow were made available following the takeover of carrier bmi by British Airways parent company IAG.
The start of the new services gives Sir Richard another chance to take on his arch rival BA - this time over UK skies.
Virgin Atlantic public relations head Fay Burgin said: "The launch of Little Red is the start of the latest exciting chapter in the history of Virgin Atlantic.
"We will be flying a total of 13 return flights a day between Heathrow, Manchester, Edinburgh and Aberdeen, giving us the scope to fly around one million passengers per year."
She went on: "The schedule of the new flights is timed to maximise connections for passengers travelling onwards from London across Virgin Atlantic's global network and Little Red will be offering a taste of the experience and customer service our long-haul passengers have come to expect.