The developments at 1 Undershaft and 22 Bishopsgate were approved by the City of London Corporation earlier this year.
Mr Khan said both would include a free public observation platform.
The 73-storey tower at 1 Undershaft, known as the Trelis, will be 305 metres (1,000ft) high - just five metres shorter than the tip of the Shard.
The Bishopsgate development comes ten years after the ill-fated Pinnacle was granted planning position.
That development was eventually abandoned, leaving a half-finished nine-storey shaft pointing towards the sky after funding dried up four years ago.
City Hall said the new developments would deliver nearly Â£6m in contributions to affordable housing, which the Corporation of London will use to deliver affordable homes on its wider estates across the city.
It will also provide more than Â£14m towards the construction of the Crossrail project.
It said the plans include a significant expansion of public open space on the sites, as well as office accommodation for almost 20,000 workers.
Mr Khan, said: "These two projects represent a significant investment in the heart of London's economy and are a clear sign that the capital is open for business.
"They will be highly-visible signs of London's enduring appeal as a place to invest.
"These new landmark buildings will offer world-class offices and it's great news that the development of the site at 22 Bishopsgate can now proceed, as this has lain unused for almost five years.
"What's more, Londoners and visitors alike should have the opportunity to take in the views from the upper reaches of these new buildings, for free, and I'm really pleased we have been able to secure this as part of the plans."
London mayor Sadiq Khan has approved the building of two new skyscrapers for the capital.