Some people have been queuing for days outside Apple and AT&T stores across the US to ensure they get hold of one of the devices.
Hundreds more are expected to start queuing during the day because stores will not start selling the iPhone until 1800 local time (2300 GMT).
Apple said buyers visiting its stores would not be able to walk out with more than two iPhones each.
Costly deal
The iPhone will be available in Europe in 2007 and Asia in 2008.
Since the iPhone was announced at Macworld in January 2007 the gadget has won a huge amount of coverage.
That interest has continued up to the launch with bloggers reporting live from queues outside some stores. Gadget site Gizmodo is broadcasting live video from the Apple store in San Francisco.
The quad-bandphone has a 3.5in (9cm) touch screen, wi-fi, no keyboard, a camera and a web browser on board. It is also intended to be used as a media player to listen to music and watch video uploaded to it via iTunes.
It is available in two versions sporting either four or eight gigabytes of memory.
Apple said the iPhone's battery was good for eight hours of talktime, six hours of net use or seven hours of video watching.
Early reviews of the iPhone have been broadly positive but those who have played around with it said touch screen typing took some getting used to and data download speeds were very slow.
The handset has also been criticised as it does not use the 3G network, does not support instant messaging or voice-activated dialling and does not let people choose ringtones beyond the 25 pre-installed on it.
Apple said it hoped to sell 10 million iPhones by 2008 and grab itself a 1% share of the mobile phone market.
To do this it will face significant competition from well-established handset makers such as Nokia and other touch screen phone makers such as Samsung and HTC.
However, some commentators thought that the high price of the gadget could put people off.
The device costs either $499 or $599 and buyers must also commit to a two-year contract with AT&T that will cost them a minimum of $59.99 per month.
As with many Apple products prices in Europe for the device are likely to be higher than direct currency conversions would suggest.
In a company-wide message relayed to Apple employees on 28 June, Steve Jobs said every worker who had been at the company for more than a year would get one of the devices for free.
The iPhone going on sale on 29 June is likely to be just the first of a long line of gadgets with future models adding the features and software lacking in the original.