The largest American branch of the Iseli Family, the origins of this group has been traced back to Hans Iseli born sometime around 1520. His three sons became half of the "founding" fathers of the Iseli von Hasle. Hans' son Benedict moved to L?tzelfl?h around 1570 where some of his children became the "founding" Iseli family in that village. Later, Niklaus Iseli moved to the hamlet of Thal, just a few miles away from L?tzelfl?h, around 1690 after marrying a local girl. Niklaus' fifth child, also named Niklaus, returned to L?tzelfl?h where Christian was born. Christian's sons were born in a number of different Swiss villages, including Wynigen.

This American Iseli Family branch is essentially the family Christian Iseli (1737) von Lützelflüh and his descendants in America. Christian and Anne Neuhaus had four sons: Johannes (1795), Samuel (1799), Jacob (1802), and Hans Ulrich (1805). With the exception of Samuel (who was a gunsmith), all the children immigrated to America. Jacob died in Elgin, Iowa; Johannes in Zoar Station, Ohio; and Hans in Trention, Ohio. In the next generation, the various spelling of the family name came into common use, probably due to the whimsy of the American immigration officials at the time. For example, Samuel's children are Christian Iseli, Jacob Iseli, John Esely, and Verena Isely.

The Iseli emigration from Switzerland to America was at several different times between 1845 and 1881. Christian Iseli, Jacob Iseli, Hans Ulrich Iseli and John Isely were among the first to come in 1845-1847. Johannes Iseli came in the Fall of 1852. Jacob Eseli came in 1870 and the John Esely Family were the last to come in 1881. They first settled in Tuscarwas County, Ohio and later moved on west to Wisconsin, Iowa, Missouri, and Kansas. Samuel Iseli spent a number of years around Vicksburg, Mississippi before coming to Wisconsin.

One example of the Iseli Family history in America is from John Isely, the eldest son of Hans Ulrich Iseli. John was born on December 12, 1826 in Burgdorf, Canton of Bern, Switzerland and immigrated to America in 1845. The family sold their farm in Switzerland and John took the money with him to purchase land. If he thought it was satisfactory, he was then to let the folks back in Switzerland know. He sent money to them in care of a relative who was to give them the word to come and use the money for their passage. This relative gave the word, but retained the money. This caused the family to have to finance their own passage which was not sufficient to allow the father, Hans Ulrich Iseli, his own room and board expenses and he was taken off the boat even as it started to move. He had to remain in Switzerland until he had funds for his own passage. The family went on but were much concerned and distressed over this matter. Hans Ulrich came later, but the ordeal of the trip together with the effects of the Malaria plague that was so prevalent in the early pioneer days proved too much for him and he died shortly after his arrival in Ohio in 1847.

The family lived in Ohio five or six years before coming to Washington Township in Green County, Wisconsin in 1852. He married Louisa Germann, the daughter of Johannes Daniel Germann and Margaritha Zurcher on May 8, 1857 and had 11 children, although many of them died at a young age. John's mother, Anna Barbara (Marti) Iseli died in Wisconsin in 1900 at age of 100 and is buried in New Glarus' (Wisconsin) old cemetery in the southeast corner of the Swiss Reformed Church yard. John died on July 20, 1878 in Oneco, Stephenson County, Illinios.

The only known history of this Family branch in America is Ralph Kenneth Gnagi's The Iseli Family Genealogy (1942). Copies can be found in the Library of Congress, the Wisconsin Historical Society Library or the Monroe County (Wisconsin) Library. The most previous section is extracted from this text. The Gnagi text errorinous identifies the first generation of the genealogy as Nieland (or Niklaus) Iseli from Zal.

Many generations of Isely's grew up and still live in the area Monroe, Wisconsin area. The life story of William Isely, grandson of John, was published in 1961 and is available at the Wisconsin Historical Society.