Between the years of 1578-1606 in which the Ottoman State had been involved in a long war with Iran and Austria, its need for the Crimean forces had increased naturally. Regardless of the deficits against the attacks of the Russian Kazakhs in the Crimea, the khans were called for participation in the military expeditions in an insistent and threatening manner (Kalgay Adil Giray participated in the military expedition towards Iran for the first time in the year of 1578 and Mehmed Giray II participated in the same expedition in the following year). The Ottoman rulers tried to treat the khans as the commanders in their retinues. All these reasons caused serious oppositions in the Crimea. Since the Ottoman Empire had been attenuated in this period, the Crimean showed this opposition with an open rebellion. Mehmed Giray II was not contented with the rebellions. At the same time, he claimed his rights about Kefe and he besieged the city. However, he was killed by the new khan, Islam Giray that was sent from Istanbul (1584). Maktul Khan's son, Saadet Giray came from the Kipchak steppe lands together with Nogay people and abducted Islam Giray. They fought with the Ottoman forces in the front of Kefe. He could not be successful in the second attempt that he tried with Nogay people and Don Kazakhs. His brother, Murad Giray penetrated into Moscow and threatened to invade the Crimea. This situation troubled the Ottoman State. Islam Giray II could establish dominion in his throne through the effective Ottoman supports. He had also delivered prayers with the name of the ruler for the first time (however, the coins were always minted in the name of Girays). Istanbul found a loyal ally in the character of Boa Ghazi Giray. He defended the empire against the Habsburg family in Hungary. Istanbul had also asked help from him against the Bandit rebellions in Anatolia. In his period, the Ottoman influence in the Crimea was reinforced again in all fields.

In the first half of the century XVII when the Ottoman Empire could not get rid of the civil turmoil and conflicts, the influence and authority of Istanbul in the Crimea had passed from a serious examination like in every other regions. Canbek Giray was enthroned as the sovereign of the khanate as a subject of the ruler for three times between the years of 1610 and 1635 and he suffered from the continuous attacks of Mehmed Giray and Sahin Giray. These two persons forcibly ascended the throne of the khanate through the collaboration with Nogay people and Russian Kazakhs in the Kipchak steppe lands. They tried to perform independent activities like their father, rival khan Saadet Giray and their grandfather, the rebellious khan, Mehmed Giray.

They had established friendly relations with Shah Abbas who was the enemy of the empire and they defeated the Ottoman forces and the khan sent from Istanbul in the year of 1610. Thus, they were able to capture Kefe. In the course of this turmoil, the Russian Kazakhs gained power and started their courageous attacks to the Ottoman and Crimean lands. They incinerated Sinop in the year of 1654. They destroyed Ahyoli in the year of 1612 and Yeniköy at the Istanbul Strait in the year of 1625. Finally, they were able to capture the castle of Azov. They also established dominion in this castle for 5 years despite the attacks of the Ottoman and Crimean forces. During the century XVII, the matter of Russian Kazakhs became a principal element not only for the Crimea, but also for the Ottoman Empire.

The period of Islam Giray III (1644-1654) was the period in which the Crimean Khanate and Ottomans established a close alliance and organised movements against their enemies in the north. He organised four big military expeditions to Russia against the Kazakhs between the years of 1644-1647. He separated Zaparog Kazakhs from Poland and attracted their interest. This was his greatest success. Through this success, he organised very successful military expeditions to Poland between the years of 1648-1653. He established political relations with Sweden against this country. However, when he concluded a peace agreement with Poland, the Kazaks took side with Russia (1654).