Ndanda Mission was founded in 1906 the Missionary Benedictine Congregation of St. Ottilien, Germany. Shortly after the arrival of the Monks of St. Ottilien, the Missionary Benedictine Sisters of the Congregation of Tutzing (Germany) also came to Ndanda. In 1908 the sisters immediately started to take care of the sick, and the chronicles of 1910 already tell about the construction of a small hospital at Ndanda.

In 1926 the old hospital was demolished and construction of a new hospital started. In 1927 the first new building was opened. This building is still in use today as Private Ward (Grade 1).
Also in 1927 Sr. Thecla Stinnesbeck OSB arrived who was the first Medical Doctor of the hospital. She would serve the population of the South East for 35 years with great dedication and zeal.

In 1970 the new main hospital wards (Ward 1 – Ward 8) buildings were opened.

In July 2004 New Operating Theatre complex was opened by the Regional commissioner of Mtwara.

At the end of 2006 the construction started of an integrated AIDS Care and Treatment/Voluntary Testing and Counselling Centre. Since 2007, all patients with HIV get their treatment there free of charge.

In 2010 the Hospital was up-graded to Regional Referral Hospital (Government Notice No: 828).

In 2014 the construction of Phase I (the Ground floor) of a new Medical Laboratory at Ndanda Hospital started. The new laboratory is in use since 2015 and was accredited with 5 stars.