Livingstone was assigned to Kuruman by the LMS and sailed in December 1840, arriving at Moffat's mission, now part of South Africa, in July 1841. Upon arrival, Livingstone was disappointed at the unexpectedly small size of the village and an indigenous Christian population, after Moffat's twenty years of work, of only about forty communicants and a congregation of 350. Reasoning that conversions would be more likely if the missionaries were themselves indigenous converts, Livingstone rapidly attached himself to the plans of missionary Rogers Edwards to found a mission farther north in territory increasingly disturbed by traders, hunters, and African settlers. Setting up the new mission at Mabotswa among the Kgatla people in 1844, he was mauled by a lion which might have killed him if it had not been distracted by the African teacher Mebalwe, who was also badly injured. Both recovered but Livingstone's arm was partially disabled and caused him pain for the rest of his life.
Dr. Robert Moffat arrived in Kuruman with his family in December 1843, and shortly afterward Livingstone married Moffat's eldest daughter Mary on 2 January 1845. She was also Scottish but had lived in Africa since she was four. After falling out with Edwards, Livingstone moved to an out-station at Chonuane among the Kwena under Chief Sechele, and finally moved with the Kwena to Kolobeng in 1847 under pressure of drought. Mary travelled with Livingstone for a brief time at his insistence, despite her pregnancy and the protests of the Moffats. She gave birth to a daughter, Agnes, in May 1847, and at Kolobeng began an infant's school while Livingstone worked on a philological analysis of the Setswana language, in which he had become fluent. The only Christian convert of Livingstone's career was made in Kolobeng when Sechele was baptized after renouncing all but his senior wife, although he was later denied communion after he took back one of his previous wives. Livingstone always emphasized the importance of understanding local custom and belief as well as the necessity of encouraging Africans to proselytize, however he always had acute difficulties finding converts he considered suited for training to be missionaries. Livingstone grew increasingly frustrated with settled missionary strategies and more willing to imagine more unconventional missionary methods. As Livingstone began to plan for new missionary initiatives, he recognized the difficulties presented by his growing family, and in 1849 he sent his family (now including daughter Agnes and sons Robert and Thomas) back to Kuruman as he planned further inland travels. Later Mary and David's family returned to England, but came to Africa again on the Zambezi Expedition.