Labor's Cressida O'Hanlon is expected to be confirmed as the next member of South Australian parliament when final votes are tallied in the Dunstan by-election.
The 51-year-old former political adviser took a 3.8 per cent two-party-preferred lead over her Liberal rival Anna Finizio in early counting on Saturday night, but must wait for pre-poll and postal votes to be tallied up to confirm her win.
The win would be a historic result for her party.
No SA government has won a seat off the opposition at a by-election in 116 years.
Premier Peter Malinauskas said he was grateful for the support of the electorate but the result would not change the government's approach.
"We've got a pretty substantial agenda that we're working our way through," he told ABC radio on Monday.
In the weeks leading up to the election, the government heavily advertised its nation-building State Prosperity Project, with billboards and wrap-arounds in the Advertiser touting its transformational green energy, hydrogen and education agendas.
The election was a vindication of Mr Malinauskas's big-picture vision for the state, Federal Treasurer Jim Chalmers said.
"That was a history-making outcome," Dr Chalmers told ABC News Breakfast.
"And really the only conclusion from that is how well that South Australian government is travelling, focused on the issues that matter to people."
Even though Labor is on track to pick up the seat and extend its parliamentary majority, the party lost ground in its primary vote.
The beneficiary of growing voter dissatisfaction with both majors is the Greens.
Candidate Katie McCusker sits on 22.4 per cent of the primary vote - a significant swing of 8.8 per cent in her favour.
In a campaign defined by the major parties slinging mud at one another's candidate, the Greens focused on policy matters such as climate, cost of living and the rental crisis, Federal Greens leader Adam Bandt said.
With the wind behind their backs, the party is now eyeing the seat of Sturt at the next federal election, SA Greens upper house MP Robert Sims declared.
But the Liberals, who held the inner-eastern Adelaide seat for 14 years under former premier Steven Marshall, are in for some serious soul-searching as they lick their wounds following the result.
Opposition Leader David Speirs has vowed to continue in the job, saying he has the support of the party.
He argued the party should emulate the formalised factional system of Labor and implement more centralised control.
"I think there needs to be a level of rigour and discipline to the way that the different groups within the party operate," he told ABC radio.
Mr Speirs said the major parties underestimated the Greens and regretted not piling as much scrutiny on them.
"We do need to take a good look at holding the Greens to account for their policy positions which many people, I don't believe, are aware of," he said.