Betting on his anti-euro, anti-migrant and anti-corruption ticket, ANO (Yes) movement chief Andrej Babis topped opinion polls by a wide margin ahead of the ballot that ends on Saturday afternoon.
"The anti-corruption drive is the key thing," said Prague pensioner Vaclav Vachel, voting ANO in the Czech capital and unfazed by a fraud indictment Babis faces for alleged abuse of EU subsidies.
"I don't like the EU at all... They're incompetent, those people in Brussels or wherever they are. They're a disaster, this (European Commission chief Jean-Claude) Juncker especially."
Far-right and far-left anti-EU parties are also expected to make strong gains which the polls suggest could lead to a fragmented parliament with up to nine parties, something analysts warn risks creating chaos and disturbing the Czech Republic's system of liberal democracy.
"This election is key to the fate of our country," Babis told reporters after casting his ballot near Prague. "I voted ANO."
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ANO has already held key posts in the outgoing rocky centre-left coalition under Social Democrat Prime Minister Bohuslav Sobotka, with Babis serving as finance minister from 2014 to May this year.
A 63-year-old Slovak-born chemicals, food and media tycoon, Babis captured around 25-30 percent support in recent surveys, putting ANO miles ahead of its current coalition partner, the left-wing Social Democrats, who scored just 12.5 percent.
'Deep dissatisfaction'
"For the first time, the majority will go to parties protesting in one way or another against the functioning of liberal democracy as we know it," the leading Hospodarske Noviny daily said in a Friday editorial.
"And for the first time we face the threat that an openly xenophobic, extremist movement will earn more than 10 percent" of the vote, it added, pointing to the far-right Freedom and Free Democracy (SPD) of Tokyo-born entrepreneur Tomio Okamura who won backing from France's far-right National Front.
The daily called the elections a "turning point... both for the country's internal functioning and its anchoring in the European Union", adding that "Czech democracy... has undoubtedly reached a critical point."
Despite their country's economic success, many Czechs who are heavily in debt or working long hours for low wages feel they have been left behind and are turning to anti-system parties to vent frustration, Hospodarske Noviny added.
With unemployment at 3.8 percent in September, the lowest level since 1998, the Czech economy is slated to grow by 3.6 percent this year.
While Babis has vowed to steer clear of the eurozone and echoes other eastern EU leaders who accuse Brussels of attempting to limit national sovereignty by imposing rules like migrant quotas, he favours a united Europe and balks at talk of a "Czexit".
Le Pen endorsement
Independent political commentator Jiri Pehe told AFP he could see "instability" or "maybe even chaos" in the wake of the vote as Babis's result could be "less glamorous than expected".
Babis's main rival, Social Democrats leader and Foreign Minister Lubomir Zaoralek, said Friday he hoped that the future government would ensure that the Czech Republic does not drift to the EU's periphery.
Surveys showed the anti-EU Communists could win 10.5 percent, ahead of Okamura's far-right SPD with 9.5 percent and the anti-establishment Pirates party with 8.5 percent.
Leader of France's far-right National Front Marine Le Pen sent Okamura a letter of support, saying that their parties want to create "a Europe of nations and liberties to which we adhere."
Okamura's staunchly anti-migrant and anti-Islamic rhetoric has surprisingly won him popularity in a country where there are hardly any Muslims.
On Saturday, voting for the 200-member lower house of parliament begins at 0600 GMT and ends at 1200 GMT, with no exit polls scheduled and results expected in the evening.
