While there are at least seven contenders for the job, the main candidates are two Italians and a Belgian seeking to replace Martin Schulz.
The German socialist is stepping down as head of the EU's only elected body to return to politics in his homeland.
Tuesday's secret ballot by 751 MEPs at the parliament in the French city of Strasbourg is most likely to be won by Italian politician Antonio Tajani, a former spokesman for Italy's scandal-plagued ex-premier Silvio Berlusconi.
Tajani, 63, who served as European commissioner for industry from 2010 to 2014, is the candidate of the centre-right European People's Party, the largest group in the assembly.
Socialist Gianni Pittella of Italy also has a shot at the top job.
But liberal Guy Verhofstadt of Belgium, parliament's Brexit negotiator, saw his chances dip after a failed merger last week with Italy's populist Five Star movement.
The winner will be in charge of the European Parliament at the critical time when it has final approval on any deal for Britain's departure from the European Union, expected in 2019.
In a febrile political climate, the result could also eventually prompt a reshuffle of other top EU jobs, an instability the 28-nation bloc can do without as it tackles crises ranging from Brexit to migration.
'Influence of populists'
For all but five years of the European Parliament's history since 1979, the EPP and social democrats have alternated in the presidency under a "grand coalition" aimed at getting laws passed more easily.
But that cozy arrangement has broken down amid a disagreement over who should succeed Schulz after his nearly five years as EU legislative leader.
EPP chief Manfred Weber said the "betrayal" by the other groups which had been expected to back Tajani means that "they are responsible for the growing influence of the populists in this house."
Pittella however has said he would not accept an EPP "monopoly" of the EU's top jobs, adding that he also opposed the German-led austerity policies aimed at tackling the eurozone crisis which critics say have wrecked debt-hit Greece and Spain.
Jean-Claude Juncker, the former Luxembourg premier who heads the European Commission, the EU's executive arm, and ex-Polish prime minister Donald Tusk, who leads the European Council of 28 national leaders, are both from the EPP.
Leftist MEPs have warned that they may push for one of those jobs if the European Parliament also ends up in the hands of conservative Tajani.
Italian politician Antonio Tajani is tipped to take out the top job. Source: AAP
Holding the key?
The key to the result may now lie with the votes of the smaller populist and anti-EU parties trying to break up the EU from within.
Eurosceptic groups led by Britain's UKIP and France's National Front made stunning gains in the last European Parliament elections in May 2014, changing the EU's political landscape.
The anti-EU movement has since gained strength, with Britons voting to leave the bloc in a shock referendum result last June, while across the Atlantic a similar wave of populism took Donald Trump to the US presidency.
Former Belgian prime minister Verhofstadt had initially been seen as having a chance, with his profile newly raised by his role as chief Brexit negotiator for the parliament, a job in which he has strongly pushed for MEPs to have a bigger role in negotiations.
But his campaign has effectively been torpedoed after he said he was considering joining forces with Beppe Grillo's Five Star movement after it defected from Farage's eurosceptic grouping.
The deal - a sign of the importance of the populists' votes - fell through when Verhofstadt's Liberal MEPs opposed any such move, especially as it came just days after the Belgian had spoken out about the threat of populism.
Tuesday's vote could go on for up to four rounds as an absolute majority in the European Parliament is needed to win the presidency.
