Labour suffered a "terrible" defeat to Plaid Cymru as the Rhondda constituency changed hands for the first time since 2003.
Leighton Andrews polled second behind Leanne Wood who secured a majority of over 3,000 votes, something Labour peer Peter Hain described as a "terrible loss" for the party.
Elsewhere, Labour had polled 18 Welsh Assembly seats by 5.45am on Friday morning as it looked to have a record fifth term in office.
With 60 seats in the assembly, a party needs to win 31 seats or more to gain an outright majority, something which has never happened since the the institution's inception in 1999.
In 2011, Labour won 30 seats.
What results have come in so far?
By 5.45am on Friday, 25 out of 40 first-past-the post results in Welsh Assembly election had been registered.
LABOUR - 18 seats
PLAID CYMRU - 5 seats
CONSERVATIVES - 2 seats
Ukip - 0 seats
Liberal Democrats - 0 seats
Labour voters "concerned" about anti-Semitism row
Party leader Carwyn Jones, who held his Bridgend seat, admitted voters had expressed "concerns" about a row over anti-Semitism in the party during campaigning.
But Labour still managed to hold seats in Swansea East, Merthyr Tydfil and Rhymney as well as in Wrexham.
Wrexham was an important win as it meant retaining Lesley Griffiths, an assembly member who was a previous cabinet minister.
'New dawn' for Wales - Wood
Following her win in Rhondda, Ms Wood said: "A new dawn is about to break in Wales. People have voted for change.
"I make a commitment tonight to serve all, whether they backed Plaid Cymru or not.
And I promise to shout loud for every single one of our communities here in the Rhondda".
'Rebuilding begins here', say Liberal Democrats
There was relief for Welsh Liberal Democrats leader Kirsty Williams who strode home to victory in emphatic style in Brecon and Radnorshire.
Ms Williams increased her share of the vote, while her 15,898 votes were more than double that of the second-place Tory candidate.
"It will take a long time to rebuild but I'm proud that rebuild begins here", she said.