The 1748 oil painting by Elias Gottlob Haussmann shows the bewigged composer aged around 60 holding the score to one of his canons.
It will be unveiled in a ceremony at around 5:30 pm (1530 GMT) in the eastern city of Leipzig, accompanied by a choir.
"Bach is coming home!" announced the Leipzig Bach Archive in April.
The work, valued at USD 2.5 million (2.2 million euros), has returned to the city after 265 years.
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"The portrait, which probably everyone has already seen once in their life, is an icon of music history and, to judge by the sources, is the only true portrayal of the composer," said the Bach museum.
"All the portraits of Bach known today stem from this one painting."
US businessman and philanthropist William Scheide -- who struck it rich at a young age from oil and devoted his life to musicology and rare books -- died in November at the age of 100 and left the painting to the Leipzig Bach Archive.
The city's annual Bach Festival also begins Friday and runs until June 21.
Best known for composing The Brandenburg Concertos, Bach was once described by the 18th century composer Ludwig Van Beethoven as "the immortal god of harmony".
Haussmann, a Leipzig painter, produced two versions of the portrait but this one, the second, is in much better condition.
The painting's history makes for colourful and beguiling reading.
Walter Jenke, a descendant of the buyer, fled Germany in the 1930s when the Nazis came to power.