During the Boshin War of 1868-69, the Tsugaru clan fought mostly on the pro-imperial side, although it did briefly join the Ōuetsu Reppan Dōmei.

Tamenobu, realizing that he would need to solicit outside help, approached the Mogami clan for an introduction to the regime of Toyotomi Hideyoshi.

The early years of the Edo era were marked by a series of major O-Ie Sōdō disturbances over the succession to the clan chieftainship.

Tsugaru Nobuhira was forced to reduce his wife to concubine status and marry a niece of Tokugawa Ieyasu to strength his political ties to the shogunate.

Nobuyoshi was forced to retire in 1655 for alleged misgovernment, and was replaced by his son, Tsugaru Nobumasa, who was a reformer who developed the resources of the domain.

Nobumasa's son Tsugaru Nobuhisa developed the arts and cultural level of the domain, but was beset by numerous natural disasters, including bad weather and repeated eruptions of Mount Iwaki.

Nobuyasu's son, Tsugaru Nobuakira attempted reforms, but was vexed by corrupt officials and died under suspicious circumstances in 1791 without heir.

Under his tenure, the official kokudaka of the domain was raised from 47,000 to 70,000 and then to 100,000 koku to cover the expenses of dispatching military forces to Ezo to protect Japan's northern borders.

Yukitsugu managed to restore order and prosperity to the domain and modernized its military forces through increased implementation of rangaku studies.

[7][8] However, it soon switched course, and was briefly a signatory to the pact that created the Ōuetsu Reppan Dōmei,[9] before backing out, once again in favor of the imperial government.

[11] After northern Honshū was pacified, Tsugaru forces joined the imperial army in attacking the Republic of Ezo at Hakodate.

[15] He later worked as a director of the Number 15 National Bank (第十五国立銀行, Dai jūgo kokuritsu ginkō), and Tsugumichi became a member of the House of Peers in 1890.