Pollsters predict he could win up to 75% of seats in the national assembly which would cement his dominance of French politics.
Polls suggest En Marche!, the fledgling party he founded only last year, may win up to 450 of the 577 seats in the national assembly, upsetting the established parties' grip on power.
That would allow him to move ahead quickly with promised legislation, including over changing labour laws to make hiring and firing easier.
Mr Macron was seen smiling, waving and taking photos with supporters who gathered outside his house in Le Touquet, northern France, as he left to vote.
In May, he scored a resounding win over far-right leader of the Front National, Marine Le Pen, in the final round of the presidential contest, winning 66.1% of the vote.
The ruling Socialist party, previously a mainstay of French politics, will face near wipe-out if the parliamentary election result mirrors the presidential one.
The Socialists dominated the outgoing assembly with 314 seats but were heavily defeated in the presidential race amid the unpopularity of former president Francois Hollande, and could win as few as 20 seats this time.
Mrs Le Pen is expected to win a seat in the assembly, but fail to capture more than six across the country for her party.
But turnout could touch record lows, in a sign of voter fatigue after seven months of roller-coaster campaigning and voting.
Less than half of the 47.5 million-strong electorate turned out for the first round last Sunday, a record low.
Mr Macron was previously economy minister in his predecessor's government, but quit the job and resigned his party's whip to launch a bid for the presidency.