Prince William will leave his job as an air ambulance helicopter pilot in the summer as he takes on more royal duties, Kensington Palace says.
The Duke and Duchess of Cambridge will "increasingly base" their family in London, it said in a statement.
Prince William said it was a "huge privilege" to fly with the East Anglian Air Ambulance, which he joined in 2015.
"I have had experiences in this job I will carry with me for the rest of my life," he said.
The royal couple and their two children are planning to move from their primary residence, Anmer Hall in Norfolk, which they will keep as a home, to their apartment in Kensington Palace.
"[They] love their time in Norfolk and it will continue to be their home", Kensington Palace's statement said.
The move comes ahead of three-year-old Prince George beginning primary school in London in September, and two-year-old Princess Charlotte starting nursery in May.
The palace said the royal couple "are keen to continue to increase their official work on behalf of the Queen".
It comes as the Queen recently stepped down as patron of 25 charitable organisations, passing some of these patronages to the duke and duchess.
Prince William has replaced the Queen as patron of the Amateur Swimming Association while the Duchess of Cambridge took the role at the All England Lawn Tennis and Croquet Club (AELTC) in Wimbledon.
The palace said these commitments "will require greater time spent in London".
Prince William's 'other job'
By Peter Hunt, BBC diplomatic and royal correspondent
This will not have been an easy decision for Prince William to make.
For a second time, he's giving up a role he didn't inherit, but gained on merit.
After stints in the RAF and the air ambulance, his days as a pilot are coming to an end.
He will miss them. He's spoken of how he's loved working in a team - something, he said, "his other job" didn't necessarily offer.
The prince is the only senior royal to have a deep understanding of the NHS the majority of the population experience.
Prince William and his wife will be available to do more royal work. The demands will increase now the Queen has turned 90.
The future king's exclusive focus will very soon be on his role as a Windsor and a destiny he'll one day embrace.
Prince William said his admiration for the medical and emergency services community "could not be any stronger".
He added: "I have loved being part of a team of professional, talented people that save lives every day."
The duke has previously described his experiences of piloting as having "some very sad and dark moments".
He told the BBC in September: "I love working as a team: that's something that my other job doesn't necessarily do: you are more out there on your own a little bit."