Julian Crampton has led the institution for 10 years, overseeing £100 million of investment in its estate and the expansion of its Hastings campus.
He will remain in post until early 2016 to give the university time to appoint a replacement.
In a message to staff, Professor Crampton said that it has been a pleasure to work in the role and that the university is in a “strong position for the future”.
“There is never an ideal moment given the many projects and developments under way across the university. However, I believe that after 10 years any institution, and perhaps especially a university, benefits from a change of leadership,” he said.
“It therefore feels the right moment for me to retire to allow the board and university to recruit a new vice-chancellor who has an opportunity to deliver on the new strategic plan, and have a full four years to prepare for the next REF in 2020 in pursuit of our research ambitions,” he added.
Lord Mogg, chairman of the university’s board of governors, said that Professor Crampton was owed “a tremendous vote of thanks” for his decade-long vice chancellorship.
“We have seen major progress in raising the academic and research standing of the university leaving it well placed to meet the challenges of the coming decade and a greatly enhanced reputation in the region and throughout the academic world,” he added.
During Professor Crampton’s time as vice-chancellor, Brighton has helped to transform several secondary schools in the Hastings area, and expanded its campus in the town.
The university has also invested £100 million in its halls of residence and research, teaching and sports facilities.
Peter Jones, head of the South East Local Enterprise Partnership, said: “[Professor] Crampton has been instrumental in not only reshaping his university and education in Sussex but also in making a huge contribution to real and sustainable economic growth across the county and beyond.”
Professor Crampton took on the helm of Brighton in 2005 from another long-serving vice-chancellor, Sir David Watson, who died last month.