The decision comes five days after the Weekend Herald broke the news that TV3 star Hilary Barry resigned from the network after 23 years of service.
The embattled boss, who was appointed MediaWorks chief in August 2014, has also been involved in a trial featuring his former employer the NZ Stock Exchange, where he will be called as a witness.
A string of long-time TV3 personalities have left under Mr Weldon's watch.
John Campbell, Hamish McKay, Paula Penfold - wife of Barry's co-presenter Mike McRoberts - and the rest of the 3D investigative journalism team, including Melanie Reid, Phil Vine, Eugene Bingham and Sarah Hall have all left or announced their departures.
Long-serving news chief Mark Jennings resigned from MediaWorks in February.
MediaWorks said the board had accepted Mr Weldon's resignation and respected his decision.
Mr Weldon said in a statement: "I wish to share the news that, last night, I notified the MediaWorks board of my resignation from my role as CEO.
"When I joined MediaWorks in August 2014, I had a mandate to lead a significant change programme to bring the business back from receivership into a position where it could once again be a strong competitor in the market, with a sound and sustainable future. It was a big brief, laden with inherent challenges, but I took it in good faith and have dedicated myself fully to the goal since.
"I have had the full support of my Board for the strategy that we have executed at every point.
"We have made significant progress as a business. Yesterday I shared with staff that in our profit growth, we have hit our Q1 targets and that, overall, audiences are growing and innovative strategies such as the introduction of Newshub have been well received and are delivering results. Yesterday, we announced a major Joint Venture deal with NBC, the first of its kind outside of the United States.
"However, I have come to a decision that the personal cost is now too high to continue in this role.
"I feel confident that I will be leaving behind a much stronger business than existed when I arrived, and hope the next chapter for MediaWorks will further strengthen the business and ensure New Zealanders continue to enjoy what it has to offer."
MediaWorks Chairman Rod McGeoch said: "The board is very grateful for Mark's success in driving change through the entire organisation and under his leadership MediaWorks has truly become an integrated company. Mark has agreed to assist the Board on strategic projects and we would like to thank him for his efforts and successes.
"The board has complete confidence that the company will continue its momentum and growth. I would like to take this opportunity to thank everyone at MediaWorks for their dedication and support of the company. I also want to assure the company and its stakeholders that the strategy initiated by Mark will continue."
MediaWorks employees were tight-lipped today at the news of Mr Weldon's resignation.
Most refused to comment, though some indicated they were happy about the news.
One said it was "good news" while another said she was "smiling". One of the employees indicated they had been told not to make public comment.
Paul Henry left the MediaWorks headquarters this morning after filming his morning show on TV3, not stopping for a New Zealand Herald reporter to comment.
Hilary Barry's 6pm news co-host Mike McRoberts also left the premises, not stopping to comment.
The company will immediately start a search for a chief executive. In the interim, MediaWorks' chief financial officer David Chalmers will act as chief executive.
Mark Weldon's CV
• Joined the MediaWorks board in August 2014 as chief executive officer managing its Radio, Television and Interactive operations
• Former NZX chief executive
• He represented New Zealand as a swimmer at the 1992 Summer Olympics in Barcelona, Spain in the men's 50m freestyle and in the 4x100m freestyle relay and at the 1990 Commonwealth Games in Auckland
• He has a Juris Doctor Degree from Columbia University, New York
• Has a Diploma in International Law (Hons) from Columbia, a MCom (hons) in Economics and Bachelor degrees in Commerce and Arts from the University of Auckland
• Weldon was made a companion of the Queen's Service Order for answering the call from Prime Minister John Key to help get earthquake-hit Christchurch back on its feet
• He has worked as an as an attorney in New York, and then as senior adviser to chief executives at a number of Fortune 500 companies for McKinsey & Company.
