Ndanda Mission was founded in 1906 by 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 describe the construction of a small hospital at Ndanda.

In 1926, the old hospital was demolished and the construction of a new hospital began. 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. She 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, a new Operating Theatre complex was opened by the regional commissioner of Mtwara.

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

In 2010, the Hospital was upgraded 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 began. The new laboratory has been in use since 2015 and was accredited with 5 stars.