The race for Farrer in southern NSW is being viewed as an electoral test of support for Pauline Hanson's populist One Nation party, which could win its first lower-house seat.
Candidate David Farley was waiting at the gates of Albury Public School as they opened at 8am to let voters through.
They will ultimately choose a replacement for former Liberal leader Sussan Ley, who quit parliament after being toppled by Angus Taylor and coalition partner David Littleproud was replaced by Matt Canavan.
After spending 23 days campaigning in the regional electorate - including 11 nights sleeping in a swag - Senator Canavan concedes voters are frustrated with a perceived lack of leadership from Canberra.
"There's no doubt people want to give the political class a kick, and this is a bit of a free kick," he told AAP on Friday while driving to the town of Corowa, where he planned to deliver donuts to campaign volunteers from all sides.
"Win, lose or draw, the great thing is being here to hear that response, to cop it on the chin, to take my medicine. I'm willing to do that."
One Nation and the Climate 200-backed independent Michelle Milthorpe appear neck and neck to replace Ms Ley but analysts believe preferences could get the populist party over the line, while coalition candidates struggle.
The Nationals leader insisted other regional coalition seats were not at risk to a One Nation surge, arguing there were unique circumstances at play in Farrer.
"By-elections are always different... it's a totally different race than normal," he said.
While Mr David Farley and Ms Milthorpe appear close in the polls, preferences from coalition voters will improve Mr Farley's chances of getting over the line, RedBridge pollster Tony Barry told AAP.
"Winning the seat on primary votes would be highly unlikely, but would be a complete boil-over if that were to occur. So preference flows will be critically important," he said.
"With the coalition preferencing One Nation, they are the intuitive choice to win the seat."
Polls have shown the Liberal candidate Raissa Butkowski and the Nationals' Brad Robertson trailing far behind.
If One Nation wins, it will show the populist party is a strong electoral force, particularly in regional areas, the former Liberal party strategist said.
"If they cannibalise the Liberal and National Party vote as expected, then it's a very safe conclusion to say that we're going to see similar voting behaviours and patterns in other regional seats," Mr Barry said.
Prime Minister Anthony Albanese said the vote was a test for Senator Canavan and his Liberal counterpart Angus Taylor, and said it would be an extraordinary outcome if the Liberals and Nationals didn't finish in the top two.
Labor isn't running a candidate in the by-election.
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