Siberia entered the flow of Russian history relatively late, at the end of the sixteenth century. The official Russian incursion into Siberia dates to 1581, when the Cossack hetman Ermak Timofeevich led a detachment across the Ural Mountains and soon after defeated the forces of the Khanate of Sibir'. The paths of Novgorodian merchants and Slavic warriors may have reached Siberia even earlier, however, as Russian settlement inexorably crept toward the land beyond "the Kamen" (an archaic name for the Urals). Even prior to Ermak's expedition, reports had circulated about the enormous wealth of the Siberian land, creating a mystique that pulled the Russians eastward.

Tsar Ivan the Terrible (Ivan IV, 1530-84) provided the great impetus in pushing the Russian border to the east. Pursuing the remnant khanates of the Golden Horde across Eurasia, Ivan sacked Kazan in 1551 and Astrakhan in 1557. The remaining large region still controlled by the heirs of Genghis Khan was in the western part of Siberia, where Khan Kuchum held the wide territory from the middle Urals to the Ob River. Ermak's troops defeated those of Khan Kuchum in a three-day battle on the Irtysh River in October 1582, an event that essentially opened the gates of Siberia to the Russians. In time, a network of fortified Russian towns and outposts penetrated ever deeper beyond the Urals. Commercial activity, spurred by traders and trappers as well as merchants such as the Stroganovs, soon established a permanent Russian presence in Siberia. The snowy and seemingly endless expanses of wilderness contained many fur-bearing species of great value in European markets. Indeed, the pelt of the sable became the symbol for the immense wealth of Siberia and continued to draw Russians to their eastern borderlands for centuries.

As Russian promyshlenniki (frontiersmen) followed in pursuit of fur, they inevitably moved east on the tributaries of the great Siberian rivers (which flow north to the Arctic Ocean) and crossed the Eurasian continent. Other Cossack explorers took a more northerly route, following the "Mangazeian waterway" along the Arctic coast from Arkhangel'sk on the White Sea to the mouths of the Ob, Irtysh, Enisei, and Lena Rivers. The Russians finally reached the shores of the Pacific Ocean in 1639, with the arrival of Ivan Moskvitin on the Sea of Okhotsk. Subsequent expeditions went on to Chukotka and Kamchatka. By 1648, Semen Dezhnev had reached the straits separating Asia and America that later were named after Bering. While it took almost another century for the Russians to cross the North Pacific, the expansion through Siberia began a process of discovery along their eastern frontier that culminated in the voyages to Alaska.