Sunday's run-off comes after neither candidate obtained an absolute majority in the first round.
France is the eurozone's second-biggest economy as well as a global military and diplomatic heavyweight, with veto power as a permanent member of the UN Security Council.
The second round has boiled down to a battle between the pro-European, pro-globalisation vision of Macron and Le Pen's hostility to the EU and NATO.
If Le Pen wins, it would further shake up the West's postwar order, already rattled by Britain's vote to leave the EU and Donald Trump's election to the White House.
The president is elected in a direct popular vote of one or two rounds.
Sunday's run-off comes after neither candidate obtained an absolute majority in the first round. Every French presidential election since 1965 has gone to a second round.
Macron won 24 percent of the vote and Le Pen finished second with 21.3 percent as France's traditional left and right parties were eliminated in the first round for the first time since the start of the Fifth Republic in 1958.
A total of 47.58 million people are registered to vote. The country's 66,546 polling stations will open at 8:00 am (0600 GMT) and most will close at 7:00 pm, while those in Paris and other big cities will remain open an hour longer.
The first estimated results could come as early as 7:45 pm (1745 GMT).
The new president will take over from Socialist Francois Hollande and is expected to be sworn in by May 14.