While the interregnum that followed the fall of Pagan Empire lasted over 250 years (1287–1555), that following the fall of First Taungoo was relatively short-lived. One of Bayinnaung's sons, Nyaungyan Min, immediately began the reunification effort, successfully restoring central authority over Upper Burma and nearer Shan states by 1606. His successor Anaukpetlun defeated the Portuguese at Thanlyin in 1613. He recovered the upper Tanintharyi coast to Dawei and Lan Na from the Siamese by 1614. He also captured the trans-Salween Shan states (Kengtung and Sipsongpanna) in 1622–26. His brother Thalun rebuilt the war-torn country. He ordered the first ever census in Burmese history in 1635, which showed that the kingdom had about two million people. By 1650, the three able kings–Nyaungyan, Anaukpetlun, and Thalun–had successfully rebuilt a smaller but far more manageable kingdom.

More importantly, the new dynasty proceeded to create a legal and political system whose basic features would continue under the Konbaung dynasty well into the 19th century. The crown completely replaced the hereditary chieftainships with appointed governorships in the entire Irrawaddy valley, and greatly reduced the hereditary rights of Shan chiefs. It also reined in the continuous growth of monastic wealth and autonomy, giving a greater tax base. Its trade and secular administrative reforms built a prosperous economy for more than 80 years.^[55] Except for a few occasional rebellions and an external war—Burma defeated Siam's attempt to take Lan Na and Mottama in 1662–64—the kingdom was largely at peace for the rest of the 17th century.

The kingdom entered a gradual decline, and the authority of the "palace kings" deteriorated rapidly in the 1720s. From 1724 onwards, the Meitei people began raiding the upper Chindwin River. In 1727, southern Lan Na (Chiang Mai) successfully revolted, leaving just northern Lan Na (Chiang Saen) under an increasingly nominal Burmese rule. Meitei raids intensified in the 1730s, reaching increasingly deeper parts of central Burma. In 1740, the Mon in Lower Burma began a rebellion, and founded the Restored Hanthawaddy Kingdom, and by 1745 controlled much of Lower Burma. The Siamese also moved their authority up the Tanintharyi coast by 1752. Hanthawaddy invaded Upper Burma in November 1751, and captured Ava on 23 March 1752, ending the 266-year-old Taungoo dynasty.