Some 1515 new firms based in the G2 postcode area registered with Companies House, marking the district out the country's start-up capital.
The EH3 area, which spans the George Square core of the University of Edinburgh and the city's affluent New Town, came some way behind in second place. It had 1277 start-ups.
The rankings are based on an analysis of Companies House numbers by the Federation of Small Businesses.
It found Glasgow and Edinburgh both had three postcode areas among the top 10 districts in Scotland based on the number of start-ups.
The country's two most populous cities accounted for six out of the seven top-ranking districts.
Two districts in South Lanarkshire made the top 10. The area including Lanark was fourth, with 821 start-ups. The district including Hamilton was eighth, with 508 new businesses.
The AB11 district in central Aberdeen had the ninth most start-ups, 484.
Dunfermline in Fife ranked tenth with 443 firms.
The Companies House data indicate the business birth rate increased in Scotland in the past year, when 30,263 registered, compared with 25,500 in the preceding period.
Andy Willox, the FSB's Scottish policy convenor, said: "The Scottish economy has had its ups and downs over the last few years and many people will have decided to start up on their own because their circumstances changed."
He added: "We need to ensure that the public and private institutions that interact with these new firms, including banks, enterprise agencies and regulators... encourage them to thrive and grow."
Hugh Lightbody, chief officer at the Business Gateway advice service said: "All reports showing an increase in the number of start-ups in Scotland are welcomed and these figures reflect the trend we are also seeing."