The All Under One Banner Event (AUOB) event will leave Holyrood at 1pm today and end in the Meadows.
It is the 21st event organised by AUOB since it launched in 2014.
More than 400 Yes Bikers are due to join the parade along with a large contingent from the Saor Alba independence pipe ban.
The Edinburgh event follows similar marches in towns and cities across Scotland, including Glasgow, Galashiels, Oban, Ayr, Aberdeen and Perth.
Organisers believe that more than 100,000 people will attend the march with hopes the figure will double that and match the turnout for the largest political demonstration in Scotland, when 200,000 marched in the capital during the G8 summit at Gleneagles in 2005.
Neil Mackay, founder of the AUOB event, said: "We know a lot of people are making a special effort to come and march and rally for independence in the nation's capital.
"We are pretty certain this will be our biggest event yet as the current political climate over Brexit and the chaos in Westminster where the Government has built momentum in the independence movement as we shall see today."
A "human saltire" event is also being held in Holyrood Park at noon, where thousands are due to recreate Scotland's national flag.