I don’t think we have any accounts of his reaction on seeing it for the first time, but he had presumably seen it from afar before conquering Constantinople. You can see it from across the Bosporus in Scutari, and the Ottomans had controlled that area since the 14th century.

During the last day of the siege on May 29, 1453, thousands of citizens of Constantinople fled there. The Greek Orthodox population had actually mostly avoided Hagia Sophia since December of 1452, when the Orthodox Church attempted to unite with the Latin Church in Rome. The church hoped that by uniting with Rome, they would receive military help from Western Europe, although they didn’t actually receive much help. So the Orthodox inhabitants hadn’t been there for months, but now they all wanted to go there, apparently because they believed a prophecy that the Turks wouldn’t reach the church - they would supposedly be defeated when they reached the Column of Constantine.

But they were mistaken. The Ottomans pillaged the city, including Hagia Sophia, and they began massacring everyone they could reach inside. Mehmed himself didn’t enter the city until later in the afternoon:

“Like the Byzantine emperors before him, he rode proudly down the Mese towards the Augousteion and Hagia Sophia, passing the piles of corpses and the ransacked houses and churches. Even Mehmed was rather taken aback when he saw for himself the magnitude of the devastation that his troops had wrought, and he is said to have exclaimed sadly, ‘What a city we have given over to plundering and destruction!’, and to have shed a tear. He did not neglect to play the role of the pious warrior of Islam, however. When he reached Hagia Sophia, he dismounted from his horse, lay face down on the earth and sprinkled a handful of dust on his turban, a gesture of humility before God, the real victor. He then entered the cathedral and instructed a muezzin to climb into the pulpit and to proclaim that there was no God but God and that Mohammed was His prophet.” (Harris, pg. 212)

He stopped the massacre although the people inside were taken captive and presumably sold into slavery. Some people may have escaped but over the next few days the Ottomans found everyone who was hiding in the cisterns under the city, presumably including those who had escaped there from Hagia Sophia. A few days after the conquest, on Friday, June 1, Hagia Sophia was used as a mosque for the first time.

I should also mention that there were stories invented by Greek and Italian survivors about what Mehmed did when he arrived there, but they are clearly not true and are meant to slander the sultan and Islam in general. Filippo da Rimini, the Venetian chancellor of Corfu, wrote that Mehmed raped a virgin on the altar of Hagia Sophia. Supposedly Mehmed did this to avenge the death of Cassandra at Troy. The Turks were commonly believed to be descended from the Trojans, who were known as “Teucri” in Latin thanks to the Aeneid, where King Teucer is the ancestors of the Trojans (but not the same Teucer who fights for the Greeks in the Iliad). It was easy enough to switch the letters around so that “Teucri” was associated with “Turci”. The Trojans/Turks therefore took revenge on the Byzantines/Greeks for the destruction of Troy and the rape of Cassandra, and Constantinople took the place of Troy (which was actually not far away, further south on the Dardanelles).

Other embellishments to this story make the girl the daughter of Constantine XI, and that Constantine’s daughter and son were both raped on the altar, even though in reality Constantine had no children. Of course Mehmed didn’t do any of this, but this is apparently what some Europeans believed had happened.

Sources:

Jonathan Harris, The End of Byzantium (Yale University Press, 2012)

Marios Philippides and Walter K. Hanak, The Siege and the Fall of Constantinople in 1453: Historiography, Topography, and Military Studies (Ashgate, 2011)