In 1843 he left Kuruman to form a new station about two hundred miles to the north-east at Mabotsa, and whilst here he married a daughter of Dr. Moffat, a girl who had lived among missionaries for many years, and so was accustomed to the rough, solitary existence which would be her lot. "My time," wrote Livingstone to a friend, "is filled up with building, gardening, cobbling, doctoring, tinkering, carpentering, gun-mending, farriering, preaching, schooling, teaching, and lecturing, while my wife, in addition to her usual work, makes clothes, soap, and candles, and teaches classes of children."
Gradually it dawned upon Livingstone that a great work awaited him in the interior, but it was a work which he must face alone. "I must not be a more sorry soldier than those who serve an earthly sovereign," he wrote to the Directors of the Mission, to whose care he commended his family. "And so powerfully am I convinced it is the will of God, that I will go, no matter who opposes."
Therefore in 1852, having seen his wife and children off to England, he started in his Cape waggon and again made for Kuruman, after leaving which he was constantly harassed by parties of Boers, who believed he was teaching their slaves to rise in revolt. But he reached the land of Sebituan, a friendly chief, safely, and found the warmest welcome awaiting him. As doctor and missionary his hands were full, and seeing the field of work opening all around him, he grew more and more anxious to become the pioneer missioner to the very interior. Fever, he realised, would be his worst enemy. "I would like," he wrote in his journal, "to discover some remedy for that terrible disease. I must go to parts where it prevails most and try to discover if the natives have a remedy for it.... I mean to open up a path to the interior or perish. I never have had the shadow of a doubt. Cannot the love of Christ carry the missionary where the slave trade carries the trader?"
The travels of Livingstone through that unknown country which he practically discovered, would have to be closely followed on a map from point to point to be made clear. Otherwise they are a mere string of strange names. He set out in the November of 1853. "I had three muskets for my people and a double-barrelled gun for myself," he said. "My ammunition was distributed through the luggage, that we might not be left without a supply. Our chief hopes for food were in our guns. I carried twenty pounds of beads, a few pounds of tea, sugar, and coffee. One tin canister was filled with spare clothes, another was stored with medicines, a third with books, and a fourth with a magic lantern. A small tent, a sheep-skin, and a horse-rug completed my equipment, as an array of baggage would have excited the tribes." Four years later, worn out by frequent attacks of fever, but otherwise perfectly satisfied with the result of his journeyings into parts where as yet no other Englishman had penetrated, Livingstone sailed for England, having heard nothing of his family for three years. He at once became the hero of the hour; dinners were given, speeches were made in his honour, and he was asked to equip and command a government expedition for the exploration of that part of South-Eastern Africa through which the river Zambesi flows. After some consideration he decided to undertake this, though it meant that from henceforth he would cease to be a missionary pure and simple. But he looked at the question in its broadest aspect. "Wherever I go," he said, "I go as the servant of God, following the leadings of His Hand. My ideal of a missionary is not that of a dumpy man with a Bible under his arm. I feel I am not my own. I am serving Christ in labouring as well as in preaching, and having by His help got information which I hope will bring blessing to Africa, am I to hide the light under a bushel, because some will not consider it sufficiently or even at all missionary? I refrain from taking any salary from Missionary Societies, so no loss is sustained by any one."