The Burmese, led by King Bayinnaung, conquered Chiang Mai, initiating a 200-year Burmese rule over Lan Na. Conflict arose over the Shan states, with Bayinnaung's expansionist ambitions leading to an invasion of Lan Na from the north. In 1558, Mekuti, the Lan Na ruler, surrendered to the Burmese on 2 April 1558.^[17]

During the Burmese–Siamese War (1563–64), Mekuti revolted with encouragement from Setthathirath. However, he was captured by Burmese forces in 1564 and taken to Pegu, then the Burmese capital. Bayinnaung appointed Wisutthithewi, a Lan Na royal, as the queen regnant of Lan Na after Mekuti's death. Later, in 1579, one of Bayinnaung's sons, Nawrahta Minsaw,^[18] became the viceroy of Lan Na. While Lan Na enjoyed some autonomy, the Burmese tightly controlled labor and taxation.

Following Bayinnaung's era, his empire disintegrated. Siam successfully revolted (1584–93), leading to the dissolution of Pegu's vassals by 1596–1597. Lan Na, under Nawrahta Minsaw, declared independence in 1596 and briefly became a tributary of Siam's King Naresuan in 1602. However, Siam's authority waned after Naresuan's death in 1605, and by 1614, it had nominal control over Lan Na. Lan Na sought assistance from Lan Xang rather than Siam when the Burmese returned.^[19] For over a century after 1614, vassal kings of Burmese descent ruled Lan Na, despite Siam's attempt to assert control in 1662–1664, which ultimately failed.