The defence of the kingdom had been largely in the hands of Saluva Narsimha of Chandragiri, and by 1485 he had seized power and managed to stay any further disintegration. His infant son was usurped soon after his own death by the regent and a new dynasty, the Tuluvas, led by Narasa Nayaka, took control in 1490, in time to wage war against the newly formed sultanate of Bijapur under the Adil Shahis. A prime cause for the battle between them was the Raichur Doab, a rich alluvial plain between the Tungabhadra and the river Krishna. 

Narsimha Raya, as he was known, extended his conquest into drauveda, the Tamil lands, and built forts at Chandagiri and Vellore. One of his sons, Krishna Deva Raya, succeeded him in 1509 and became over the next 20 years Vijayanagara's greatest military leader and monarch. Under Krishna Deva Raya the kingdom of Vijayanagar reached its peak of power and sophistication. His half-brother Achyuta Raya, lacked all his qualities and lost all his property and prestige, failing to control the intrigues of rama Raya, son of Krishna Deva Raya's minister. 

On the death of Achyuta in 1542 and that of his infant son, Rama Raya seized power in the name of Krishna Deva Raya's own young son, Sadashiva, forcibly replacing the earlier Brahamani administrative with his own adherents. He successfully allied himself first with one Deccani ruler then another in order to make joint attacks on Bijapur, then Ahmednagar. Such chicanery and savage treatment by the Hindus of conquered Muslims decided the Deccani Sultans to form a confederacy to crush rama Raya's overweening power, and in 1565 the battle of talikota took place.

The Hindus were completely rooted on the death of Rama Raya; they fled the field and fled Vijayanagar on their elephants, with countless treasures, leaving their glorious city open to robber tribes and to the vengeful Muslims. 'No retreat, no flight was possible except to a few, for the pack-oxen and carts had almost all followed the forces to the war, and they had not returned ... for a space of five months Vijayanagar knew no rest. The enemy had come to destroy, and they carried out their object relentlessly..... Never perhaps in the history of the world has such havoc been wrought, and wrought so suddenly, on so splendid a city; teeming with a wealthy and industrious population in the full plenitude prosperity one day, and on the next seized, pillaged, and reduced to ruins, amid scenes of savage massacre and horrors beggaring description.