Although Amani was only gazetted as a nature reserve in 1997, research in the area began a century earlier when the Germans established a research station and botanical gardens here. Large areas of forest were cleared and numerous new species introduced. Within a few years the gardens were the largest in Africa, totalling 304 hectares and containing between 600 and 1000 different species of plants, including many endemic species. Soon thereafter, exploitation of the surrounding forest began and the gardens began to decline. A sawmill was started and a railway link was built connecting Zigi, about 12km below Amani, with the main Tanga–Moshi line to transport timber to the coast.

During the British era, research shifted to Nairobi, and the railway was replaced by a road linking Amani with Muheza. Many of the facilities at Amani were taken over by the nearby government-run malaria research centre and the gardens fell into neglect.

More recently, thanks to funding from the Tanzanian and Finnish governments and the EU, projects have been underway to promote sustainable resource use by local communities. Local guides have been trained and visitor access to the eastern Usambaras has improved thanks to Amani's trail network.