Louise Jeffreys will step down as the artistic director of the Barbican after nine years in the role.
She will leave the post at the end of the year although a replacement is yet to be announced.
Jeffreys joined the London venue in 1999 as its head of theatre and arts projects, becoming artistic director in 2010.
She oversaw increased footfall at the renowned centre of performing arts in the Barbican Estate of the City of London.
Some 1 million tickets are now sold annually and the venue counts 70,000 Young Barbican Members aged between 14 and 25.
The centre, famed for its brutalist architecture, contains concert halls, cinemas and gallery spaces, and has in recent years hosted work by US artist Jean-Michel Basquiat as well as the London Symphony Orchestra conducted by Sir Simon Rattle.
Jeffreys said she would “miss and cherish” her time at at the Barbican.
She said: “My creative home for 21 years, the Barbican has given me many opportunities to grow and develop.
“However, nothing would have been possible without collaborating with amazing artists, organisations and communities – and the wonderful team of talented and committed people with whom it’s been a huge privilege to work.
“I will miss and cherish it enormously.”
Sir Nicholas Kenyon, managing director of the Barbican, said: “We will be very sad to see Louise leave the Barbican; she has been such a force for good in the organisation over more than two decades and has led its artistic work to a peak of success which has gained the widest acclaim.
“She has passionately and tirelessly championed best practice in the arts and has developed the Barbican to a new awareness of its civic role. We will miss her greatly as she moves on.”
Giles Shilson, chairman of the Barbican Board, said: “Louise has been a passionate advocate for both the Barbican and the arts in general, and will be greatly missed.
“I’m delighted that we will still have the pleasure of her company for the next few months and on behalf of the Barbican Centre Board, wish her the very best for all her future endeavours.”