During the rule of Boris Alexandrovich in the first half of the 15th century Tver experienced the last rise of its power as a center of independent principality. Big-scale construction was started then. A stone prince's palace, the second in time after the Bogolyubsky in Northeastern Rus, a stone cathedral belfry (1407) and stone churches of John the Merciful (1420), Boris and Gleb (1438) and Michael - Archangel (1455) were built in the Kremlin; stone temples were built in Fedorovsky and Zheltikov monasteries. The economic rise of the city was accompanied with vast economic relations and diplomatic activeness (journey of A. Nikitin, participation of Ambassador of Tver Foma in the Council of Florence).
In 1485, Moscow troops occupied Tver and Prince Mikhail Borisovich fled to Lithuania. The Tver Principality ended the independent political existence and entered the Russian centralized state being formed at that time. Between 1485 and 1490, Tver was a domain of Ivan Ivanovich, son of Ivan III. Afterwards, governors of the Great Prince started governing the city.
At the end of the 15th - 16th centuries, Tver remained a big trading and craft center and significant stone construction was done in the city (the Church of Trinity over the Tmaka River, the so-called "White Trinity" survived). In December of 1569, Tver was looted by the oprichnik (life-guardsmen) troops of Ivan IV the Terrible that were marching to Novgorod. In the period of social, economic and political crisis experienced by the Russian state at the beginning of the 17th century Tver was exposed to attacks of the Polish-Lithuanian invaders. In 1606, residents of Tver parried the attack but in 1609 the invaders managed to seize Tver. In the same year Prince M. V. Skopin-Shuisky moving with the troops from Novgorod to Moscow drove the occupants out of Tver. As a result of the Polish-Lithuanian "devastation" Tver grew desolate.
Bearing in mind the importance of the strategic position of the city on the route from Moscow to Novgorod, the government of Czar Mikhail Fedorovich appointed D. P. Pozharsky-Lopata on the post of the voivoda in Tver. In a short period of time he managed to restore the fortifications destroyed during the "turmoil." In the middle of the 17th century, Tver mostly recovered from consequences of the Polish-Lithuanian intervention. The archbishop yard ensemble was built in the Kremlin and stone Vladimir tower was erected (1674, it was located opposite to the contemporary House of Officers) and a shopping arcade with stalls was built on the square in front of it, the cathedral of the city was rebuilt in 1696. The smith craft was developed in Tver further. The Streletskaya and Yamskaya settlements were arranged on the territory of the Zagorodsky suburb.