Arsenal managing director Keith Edelman will leave the club "to seek pastures new and embark upon fresh challenges".
Edelman departs after eight years at Arsenal in which he played a key role in their move to the Emirates Stadium.
He was responsible for commercial and administrative activities and oversaw Arsenal's turnover breaking £200m.
"Under Keith's stewardship the Club has achieved record profits and the Board owes him a debt of gratitude," said Gunners chairman Peter Hill-Wood.
"Keith has played a major role in the growth of the club since he joined in 2000.
"In that time we have successfully implemented the move from Highbury to Emirates Stadium that has underpinned the future of the business and confirmed our position as one of Europe's leading clubs."
Edelman has fiercely and repeatedly rejected claims that Arsenal require outside investment to compete with Manchester United, Chelsea and Liverpool - their closest Premier League rivals who are all foreign-owned.
"The board has already initiated the search for a new managing director and will update shareholders and stakeholders when appropriate"Arsenal have been subject to takeover rumours with Red and White Holdings Limited, which is jointly owned by Russian billionaire Alisher Usmanov and London-based Farhad Moshiri, upping its stake in the club to 24% to become the largest shareholder ahead of director Danny Fiszman.
American billionaire investor Stan Kroenke, meanwhile, holds a 12% stake.
Edelman is reported to hold only a nominal number of shares but his exit could spark fears of a fresh takeover bid.
"I have thoroughly enjoyed my time at Arsenal," said Edelman.
"It has been a very exciting period for the business and I am proud to have contributed to the club's many off-field achievements over the past eight years, not least the Emirates Stadium project.
"Now that we have completed our second season at Emirates, I believe it is the right time to seek pastures new and embark upon fresh challenges."
After his arrival at the north London club, Edelman completed the first strategic partnership Arsenal had entered into since forming when a 10% stake was sold to Granada Media for £77 million.
606: DEBATEHe oversaw Arsenal's re-branding and crest redesign and was later engineered a new sponsorship deal with Nike, valued at £130 million over 10 years.
With the stadium nearing completion, Edelman completed one of the largest football sponsorship deals, with Emirates Airlines for over £100 million, including naming rights to the ground.
"The board has already initiated the search for a new managing director and will update shareholders and stakeholders when appropriate," read a statement from Arsenal Holdings PLC.
"In the meantime, director Ken Friar, who has a wealth of football-based experience and business acumen having previously occupied the role of managing director (1982-2000), will assume the position of acting managing director."
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