The Akwamu like most Akans migrated from Adanse to settle at the Twifo-Heman forest at the later part of the 16th century. They gained much of their wealth from trading with European merchants. This group of Akans belonged to the Aduana family and are blood brothers of Asumennya, Dormaa and Kumawu. According to oral tradition it was as a result of succession dispute that compelled Otomfuo (brass-smith) Asare to desert the family to form a new state or city called Asaremankesee: Asare's big state. The modern city of Asaamankese was originally founded and occupied by the Akwamu.
Akwamu expansion started between 1629 and 1710 and this took them to places like the whole Akuapem area including Kyerepon and Larteh, Akyem, Denkyera, Ga-Adangbe, the Ladoku states of Agona, Winneba, Afram plains, southern Togoland and finally Whydah in present Benin. Akwamu expansion allowed them to dominate trade between European forts in Winneba and Accra. The powerful king Nana Ansa Sasraku I, ruling from 1660 to 1689, fought wars of expansion but maintained amicable trading relations with European merchants. During 1710 Akwamu grew to become the largest Akan empire. Ansa Sasraku annexed the Guans and took over the traditional areas of the Kyerepons and ruled over them until Asonaba Nana Ofori Kuma and his followers after a succession dispute in their effort to form their own state engaged them in a fierce war after which the Akwamu were driven away from the mountains.
These Asona family members and their followers then were given a piece of land from the original settlers the Guans, Kyerepons, to form the Akuapem state. However, most of the present Akuapems still have their roots at Akwamufie especially those bearing the names Addo and Akoto or from the Aduana family.
Nana Ansa Sasraku also played an important role in the life of the King Osei Tutu of Asante. He protected him from the Denkyira and when he was called to take over the Kwaaman stool Nana Ansa Sasraku provided him with 300 Asafomen from Akwamu to guide him to Kwaaman. When Nana Osei Tutu arrived, he gaved all the men to Kwaaman Asafohene and they became citizens of Asafo and that won the Kumasi Asafohene the title Akwamuhene of Kumasi. According to oral tradition, the whole structure of the Asante army that was started by Nana Osei Kofi Tutu I and helped the Asante through many wars, was a replicate of the well organised Akwamu army.
Nana Osei Tutu was also assisted by the Anumfuo (later Adumfuo) who accompanied him from Akwamu, in execution cases. A large number of the Asante of today originated from Akwamu especially, people from Asafo and Adum as well as sections of people from Bantama and Barekese.
After the death of Nana Ansa Sasraku, he was succeeded by two kings collectively, Nana Addo Panin and Nana Basua. It was during this time that the Akwamu took over the possession of the Danish Castle at Christianborg or Osu.
Because of the cordial relationship that existed between Akwamu and Asante, during the 19th century expansion of Asante, the Akwamu unlike most states after war, was never annexed by Asante but rather the Akwamu Stool became the wife of the Asante Stool during the reign of Nana Odeneho Kwafo Akoto I. That is the reason why during the Golden Anniversary of Nana Kwafo Akoto II Nana Opoku Ware II crossed the Pra river to spend two days at Akwamufie.
At the peak of their power the Akwamu had embraced much of the Gold Coast and traditionally the Akwamuhene still has the jurisdiction of the Akosombo part of the Volta River. It is believed that by 1730, Akwamu was defeated by Akyem losing its power. However, as recorded in 1744, the Akwamu sold a copious quantity of slaves that were traded inland. During the 18th century, Akwamu lost its greatness and reputation, and most of their lands fell into the possession of the Akuapem, Akyem, Kwahu, Fante and Krobo.