The sudden increase in the English cost of living may have caused them to make their decision to go to America as well as religious reasons. He came against the wishes of his family and settled in Newton, Massachusetts instead of Long Island where he had friends. He came as a Free Man and paid for the passage of himself, his wife and daughter. He was classified as a Yeoman in England and there was no doubt that he was a member of a family who had been large land owners at one time. He was listed under the heading of "Outdwellers toward Saxtead" on page 55, as dwelling on the same street as Nicholas Danforth. Robert Hawes in his "History of Framlingham, Suffolk County" says in the book that Nicholas Wythe held 89 acres wit four other men. In the year of our Lord 1642 or 1643 the Wythe (Wyeth) family left England and landed in America and settled in Massachusetts where on January 7, 1644 Nicholas made his confession which could be found in the New England Historical Society papers. He became a Proprietor at Cambridge on May 20, 1645 and he bought a dwelling house and 1/2 acre of land from Robert Daniell. It was on the westerly side of Garden Street near Phillips Place, which remained in the Wyeth name for more than 2 centuries. Wyeth Street, near Harvard College, is named in his honor. In the same year he purchased from George Williams 2 more acres in Westfield and he received a grant of 6 acres. Nicholas was left to mourn the death of his sons, his wife and his friend Nicholas Danforth.

"Hence I came to New England being persecuted and courted for going from the place where we lived and hence I used means to come hither where we might enjoy more freedom". Nicholas makes reference to many difficulties before and during his cross Atlantic voyage. He also mentioned that "God took away my son" at this point. It is not clear whether the boy died during the trip or when he was planning to leave England because those who were trying to discourage him from going used the death as an excuse that "the Lord was displeased for going on".