How did settlement of the southern colonies differ from settlement of the new england and middle colonies? unlike the new england and the middle colonies, the main reason people settled the southern colonies was to gain religious freedom. unlike the new england and the middle colonies, the main reason people settled the southern colonies was to make money. settlers had many reasons for coming to southern colonies, whereas people settled in the new england and middle colonies only to have religious freedom. settlers had many reasons for coming to southern colonies, whereas people settled in the new england and middle colonies only to make money.