Among the distinguished guests who will perform are the Concertgebouw Orchestra of Amsterdam, the Accademia Santa Cecilia in Rome, the London Royal Philharmonic and conductors Antonio Pappano and Mariss Jansons.
The rising Chinese piano star Yuja Wang will play with the Pittsburgh Symphonic Orchestra.
The festival is expected to draw some 120,000 spectators, including 20,000 people from outside Romania.
"It is very rare to see such a density of top musicians over such a short period," Ioan Holender, the former director of the Vienna State Opera, told AFP.
Romanian-born Holender is acting as artistic director of the festival and has been trying for years to make Enescu's music better known around the world.
Enescu was born in the village of Liveni in northern Romania to a family of 12. His first violin lessons came from a local Roma fiddler.
He entered the Vienna Conservatory at the age of 7, graduating with distinction as a violinist at the age of 10.
He played to Brahms and knew Bartok, Strauss, Ravel, Debussy and Shostakovich.
Acclaimed internationally as a violinist, he was less known in the West as a composer though he wrote operas like "Oedipe", rhapsodies and symphonies inspired by Romanian traditional music.
In 1958, the Enescu festival was set up in Bucharest to pay tribute to his music.
The biennial festival was banned by the communist regime in 1971 but came back to life after the fall of dictator Nicolae Ceausescu in 1989.
During the festival, concerts will also take place on the streets, in cafes and even in tribunals. Contemporary artists will expose their works in public squares.
One Bucharest bakery has even launched a traditional covrigi, a traditional Romanian pretzel, in the shape of a musical clef.
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