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.
In his statement this morning, Mr Weldon said: "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."
Mr Weldon notified the board just hours after he launched MediaWorks' new channel, Bravo, a joint venture with NBC Universal which will replace Four in July, marking the end of the channel's 19-year history.
Mr Weldon was barely audible and mumbled his words at the launch event, which was a far cry from the confident and somewhat dazzling display he put on at the 2015 new season launch, just over 18 months ago.
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."
The company will immediately start a search for a CEO. In the interim, MediaWorks' CFO, David Chalmers will act as CEO.
On Monday MediaWorks said Barry's exit from TV3 had not dented Mr Weldon's position and that the board of directors had given him "full support" after a key meeting.
Mr McGeoch dismissed speculation about Mr Weldon's position following the meeting, saying every mainstream media company in the world was undergoing significant change.
He said the changes involved major restructuring which included a focus on reducing costs. Part of that was reviewing the profitability of shows.
"MediaWorks is no different. We have to change and we are changing. We have a clear strategy for this, led by our CEO." He said there was "full support for the CEO executing that strategy".
Mr Weldon has been involved in a trial featuring his former employer the NZ Stock Exchange, where he will be called as a witness.
MediaWorks employees were tight-lipped today, with most refusing to comment. However, 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'd been told not to make public comment.
A few high-profile employees, including Paul Henry and Mike McRoberts, have been spotted driving out of the building, but were unable to be stopped for comment.