It is only eight months since the previous election when his party, Sinn Fein, came second to the Democratic Unionist Party (DUP), whose leader, Arlene Foster, became First Minister. Because of McGuinness's decision and the power sharing nature of the Assembly, she also loses her post.
This dramatic event will cause concern for many due to the fragile political situation in Northern Ireland, where the two parties share power, despite having bitterly opposing politics steeped in the country's history of sectarian violence.
The incident which has led to his resignation is a scandal over the Renewable Heat Incentive scheme, which was so badly conceived and executed by the department of which Foster was then the minister responsible, that it looks likely to cost taxpayers millions.
There are allegations of incompetence and even corruption. Although all political parties have agreed there should be some kind of inquiry, the sticking point is that Foster has refused Sinn Fein's demand that she step down while it is being carried out
Under the terms of the Good Friday Agreement of 1998, devolved governments of Northern Ireland share power.
In practice, this has meant that the two parties with the least in common have dominated successive governments: the Democratic Unionist Party and Sinn Fein.
The DUP is dedicated to remaining a part of the United Kingdom, while the republican Sinn Fein -- once the political wing of the IRA -- seeks a united Ireland.
The DUP, almost exclusively Protestant, is on the right and Sinn Fein, almost exclusively Catholic, is on the left.
Working relationships at risk
They evince a bitter distaste for one another's cultures. Their instincts are to be on the opposite side of every contentious issue, like Brexit, which was backed by the DUP.
Yet for the last 10 years, there have been working relationships between McGuinness and three DUP leaders: first and most notably Ian Paisley, an octogenarian evangelical rabble-rouser, who bore a great deal of responsibility for stirring up the sectarian hatred which helped to kickstart "The Troubles" in the late 1960s.
Yet Paisley responded so well to McGuinness's skillful flattery that they achieved a warmth that charmed those outside Northern Ireland who wanted to believe the irreconcilables had reconciled, though the basic sectarian fault-line in government and Northern Irish politics remained the same.
There has been no warmth, but a business-like arrangement with Paisley's successor Peter Robinson, and, since December 2015, Arlene Foster has made it possible for the two parties to work together and look beyond this fault-line.
Scandal has widened
The dispute over the RHI was serious, but almost certainly would not have become critical had it not been that recent reports McGuinness is undergoing tests concerning his health.
In his absence, Gerry Adams, the President of Sinn Fein, has handled developments aggressively and the already stubborn Mrs Foster has in response been equally uncompromising.
McGuinness's resignation takes effect on Monday, and as things stand there is little chance that the election can be averted through compromise.
The Northern Irish electorate is furious about the waste of public money, but almost certainly the DUP will rally behind their leader to keep Sinn Fein in second place, and the mutual loathing of the two main parties will intensify.
Should McGuinness have to leave politics for good, things can only get worse.