CMS already sent his first missionaries Samuel Gobat, a Swiss Lutheran, and Christian Kugler to Abyssinia, East Africa in 1829. As Kugler died in Tigre in 1830, his place was supplied by Isenberg as a CMS recruit. Isenberg joined Samuel Gobat, a Swiss Lutheran, in Cairo, Egypt, and studied Amharic and Arabic language. In 1834, he joined the mission station at Adowa, Ethiopia where they stayed till 1838; however, Gobat was compelled to quit the mission from ill-health at Tigre, also spelt Tigray. After the departure of Gobat, he was joined by his fiancee Henrietta Geerling, Charles Henry Blumhardt, another missionary, and Johann Ludwig Krapf, a German Lutheran and missionary to East Africa, in 1837. They taught and converted a few boys, who were in-turn expelled by the Ethiopian Orthodoxy clergy. He spent his years between 1834 and 1838 at Adowa and Tigray. Unlike Gobat with whom he initially served in Ethiopia, he kept a social and cultural distance from Ethiopians. From 1838, he and fellow-missionaries faced obstacles thrown in their way by the native priesthood, especially expressed his differences with the beliefs and practices of the Ethiopian Orthodox Church in blunt. Sometimes with direct terms that the Orthodox Christian clergymen found offensive. In March 1838, he was expelled from the country due to his inability to reach any accommodation with Ethiopian Orthodoxy clergymen and unwillingness to accept the Gobat's advice over the location of the mission. In 1839, he along with his new fellow missionaries Johann Ludwig, Krapf, and Carl Heinrich Blumhardt removed the mission station to Shoa, Ethiopia, where he spent for four months before leaving for London; later, he was responsible in mission expulsion from Ethiopia in 1843 forever—In 1842, when Isemberg returned to Shoa, his mission was refused entry forcing him to turn his attention to Tagray again. However, his expulsion in June 1843, effectively ended CMS activities in Ethiopia.
With no possibility of return to Ethiopia, he was transferred to the CMS mission in Bombay, Western India – Bombay Presidency. In Bombay, he devoted most of his missionary work to a settlement for freed African slaves, some of whom returned to Africa after being trained as evangelists. Having diagnosed as terminally ill, he left India to Germany in 1864; later, died at an age of fifty-eight on 10 October 1864 at Kornthal, near Stuttgart, Germany.
Works
Grammar of the Amharic language.
Dictionary of the Amharic language.
A small vocabulary of the Dankali language.
Dictionary of the Amharic Language in Two Parts, Amharic and English, and English and Amharic.
Journals of the Rev. Messrs. Isenberg and Krapf, missionaries of the Church missionary society:detailing their proceedings in the kingdom of Shoa, and journeys in other parts of Abyssinia, in the years 1839, 1840, 1841, and 1842.
