With Ivan the Great's overthrow of the Tatars, Russia became a sovereign nation once again. This time Moscow served as the capital, and the rulers came to be known as the Muscovite dynasty. These rulers were the last group of rulers from the Riurik lineage. This period begins with Ivan the Great's rule, although Moscow had been steadily growing in importance before Ivan the Great began his reign. He took his title of Grand Prince seriously, and set out to conquer and rule Russia. He first defeated the princes of surrounding cities and replaced them with people loyal to him. Especially important were his victories over Novgorod and Tver, which rivaled Moscow in importance. While fighting to add to Moscuvy's territory, Ivan the Great remained on good terms with the Tatars, paying tribute. However, in 1480 Ivan the Great announced his sovereignty and the Tatars responded by sending forces to Moscow in an attempt to regain control of the city and its territories. The Tatars were not met with the enforcements they were expecting and retreated after a seven month stand off. This then began the official freedom of Russia from Tatar rule.

Moscow began to grow in importance with the reign of Ivan I, or Ivan Kalita. Ivan I bought villages and the land of bankrupt princes to increase his territory. The head of the Russian Orthodox church was also moved to Moscow during this time. So, while Moscow didn't yet have political authority over the whole land, it had religious authority through the church. Ivan's practice of accruing land was continued by his successors.

The reigns of Ivan the Great and Vasilii III were a time of growing power and prestige for Moscow. Ivan the Great added to his prestige in more ways than just militarily. He married Sophia, a niece of the last Byzantine emperor, Constantine XI. This move also elevated his position as Grand Prince and he sometimes used the title of tsar. His son, Vasilii III continued many of the same policies begun by Ivan the Great. He acquired the remaining Russian territories and had ties with the Holy Roman Empire. Ivan the Great and Vasilii III maintained strict control over the princes and boyars. They forbid the boyars to switch allegiance to a different prince or country, calling this treason.

Ivan the Terrible succeeded Vasilii III and was the first Grand Prince to have himself officially crowned tsar. With his reign, Russia became a fully autocratic state. He succeeded to the throne at the age of three and regents ruled for him until at the age of 16 he had himself crowned tsar. He also married Anastasia who was a member of the Romanov boyar family.

As a boy, Ivan IV suffered under the regents. While he was treated with respect in public, in private he was often neglected and tortured. He also witnessed the boyars fighting to come to power. These two things are believed to have caused Ivan IV to be cruel. As a child he was known to torture animals, and as an adult his actions earned him the name Ivan the Terrible. He was also very suspicious of the boyars and heavily persecuted them. This too may have been from seeing the actions of the boyars when he was a child.

Ivan IV's reign is usually divided into two parts. During the first half, the good period, Ivan IV ruled with the advise of a council. In 1549 he called together a zemskii sobor, assembly of the land, and then in 1550 established a new law code. He also updated the army and was initially successfully in military matters, defending Russia's borders to the east. However, he suffered losses when trying to expand his territories westward. The second half of Ivan IV's reign is known as the bad period. During this time he discontinued using a council of advisors and became especially suspicious of the boyars. He gained the authority to rule with complete autonomy when he threatened to abdicate the throne but was asked to continue his rule. This threat was calculated by Ivan IV to give him more power and he got it by agreeing to remain in power but only if he could rule without the moral guidelines of the church. After this, Russia was divided into two areas. In the region known as the oprichnina Ivan IV had sole control. In the other, the boyar Duma was to have direct rule. This agreement was never carried out though and Ivan IV had sole rule over the entire nation. He used the Oprichniki, a militia which was loyal to him to terrorize the country. Ivan IV became famous for torturing and executing thousands of people. Even members of the Russian Orthodox church were not exempt from Ivan IV's executions. The church had traditionally been a check on the power of the rulers, however when church leaders expressed disagreement with Ivan' IV's policies they were often tortured and executed. Ivan IV was a member of the Russian Orthodox church and he offered prayers for those he had executed.

During this time, people were required to give more and more to the state. Boyars lost much of the power they had had in the past. The taxes and services they were required to provide were increased. The peasants too were affected as they became officially tied to the land, making them serfs rather than peasants. In the past, the peasants usually owned the land that they worked and were able to move about freely. However, during this time land was often given to people as rewards. When the land was given, all the people on it were also given. In the beginning, the people could still move about freely during certain periods of the year. This time was gradually shortened until in 1581 the people were completely forbidden to leave the land.

Ivan IV murdered his elder son and heir which resulted in his younger son Feodor succeeding Ivan IV to the throne. This brought about the end of the Riurik dynasty as Feodor was a weak ruler who did not produce an heir to the throne. At Feodor's death, a period known as The Time of Troubles arose which was finally ended with the election by the boyars of Mikhail Romanov and the beginning of the Romanov dynasty.