As much of the territory of the middle colonies, including Pennsylvania, New Jersey, and Delaware, was given to Quaker William Penn, many of the new residents of this vast area were Quakers from Great Britain. Many Quakers were also given land grants (such as the Snowdens) or simply migrated (the Ellicotts) to nearby Maryland.

The Quakers primarily moved to the colonies, as earlier the Puritans had to New England, to escape religious persecution in Britain. The persecution in Britain was often severe, as Quakers were seen as enemies of the state. The late seventeenth century was also the heyday of British Quakerism, when there were many more there, both in actual numbers and as a percentage of the population, than today. There were also many more Quakers in the middle colonies than exist in the comparable states today.

Penn, understanding the sufferings of religious minority groups, insisted on religious tolerance and invited in such persecuted groups as the German anabaptists. Thus, German speaking peoples settled in large numbers, becoming the Pennsylvania Dutch (Deustch, meaning German). As much of the territory had originally been settled by the actual Dutch, a strong Dutch influence remained. Scots-Irish, also feeling persecuted by the British, who wanted to contain (and in some cases wipe out) militant groups in those areas, also migrated to the middle colonies. Some Italians and Portuguese came. The new migrants were largely northern (with a few southern) Europeans, forming a vibrant mix from that part of the world. Those not arriving for religious reasons were seeking economic opportunities not available to them in Europe.