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In 1888, Pangani was the center of an armed movement to resist German colonial conquest of the mainland Tanzanian coast. The local leader of the resistance was Abushiri ibn Salim al-Harthi, a Swahili-speaker born in Zanzibar who owned a small estate at the suburb that now bears his name. Abushiri was instrumental in coordinating resistance to German conquest along much of the coast. The Germans hanged him at Pangani in December 1889.

Several historical sites in and around the town serve as reminders of the strong Arabic influence and later colonial era of German East Africa and British Tanganyika Territory. The district boma or headquarters is the most impressive building remaining from the period of Zanzibari rule.