The civil defence authority said on Twitter that emergency teams were sent to the scene after a "crane fell at the Grand Mosque."
That came about an hour after it tweeted that Mecca was "witnessing medium to heavy rains," with pictures circulating on social media showing lightning.
Authorities have not yet released an official account on what happened.
Pictures of the incident on Twitter showed bloodied bodies strewn across a courtyard where the top part of the crane, which appeared to have bent or snapped, had crashed into the several storey-high building.
The incident occurred as hundreds of thousands of Muslims gathered from all over the world for the annual hajj pilgrimage expected to begin on September 21.
The Grand Mosque is usually at its most crowded on Fridays, the Muslim weekly day of prayer.
It houses the Kaaba -- the massive cube-shaped structure towards which Muslims worldwide pray.
The governor of Mecca region, Prince Khaled al-Faisal, has ordered an investigation into the incident and was heading to the mosque, the official @makkahregion page on Twitter said.
No details were immediately available on the nationalities of the victims.
But Iran's official IRNA news agency, quoting the head of the Hajj Organisation, said that 15 Iranian pilgrims were among those injured.
Most of them were treated as outpatients, Saeid Ohadi said.
A massive project is currently underway to expand the area of the mosque by 400,000 square metres (4.3 million square feet), allowing it to accommodate up to 2.2 million people at once.
The mosque is surrounded by a number of cranes.
The official SPA news agency said in a statement that by Friday, almost 800,000 pilgrims had arrived into the kingdom for hajj.
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