The last war of Ivan's reign was instigated by Ilham's widow, who married Moxammat Amin and persuaded him to assert his independence from Moscow in 1505. The rebellion broke out into the open on Saint John's Day, when the Tatars massacred Russian merchants and envoys present at the annual Kazan Fair. A huge army of the Kazan and Nogai Tatars then advanced towards Nizhny Novgorod and besieged the city. The affair was decided by 300 Lithuanian archers, who had been captured by Russians in the Battle of Vedrosha and lived in Nizhny in captivity. They managed to put the Tatar vanguard into disarray: the khan's brother-in-law was killed in action and the horde retreated.

Ivan's death prevented hostilities from being renewed until May 1506, when Prince Fyodor Belsky led Russian forces against Kazan. After the Tatar cavalry attacked his rear, many Russians took flight or drowned in the Foul Lake (22 May). Prince Vasily Kholmsky was sent to relieve Belsky and defeated the khan on Arsk Field on June 22. Moxammat Amin withdrew to the Arsk Tower but, when the Russians started to celebrate their victory, ventured out and inflicted an excruciating defeat on them (June 25). Although it was the most brilliant Tatar victory in decades, Moxammat Amin – for some reason not clearly understood – resolved to sue for peace and paid homage to Ivan's successor, Vasily III of Russia.