In the spring of 1855, Alexander and Robert Hill, brothers from Mill Creek in Salt Lake Valley, drove a herd of range cattle over the mountains from Malad Valley to Cache Valley. They built a cabin at the site of Mendon and started farms. In 1856 William Gardner and his family settled to the south of the townsite at Gardner's Creek.
Spring of 1859 saw the beginning of a great influx of settlers from the Mill Creek and Big Cottonwood areas to North Settlement (beyond Maughan's Fort). Most were immigrants from England, Scotland, and Denmark. Others came from the Atlantic coast, the Midwest, and Canada. They included the Anderson, Atkinson, Bird, Farr, Findley, Forster, Gibson, Jensen, Larsen, Lemmon, Luckham, Shumway, Sorensen, Sweeten, and Willie families. According to E.W. Tullidge, the date of arrival was 2 May 1859. Charles Shumway, a member of the Council of Fifty, served as LDS presiding elder, with James Willie, recent captain of the ill-fated Fourth Handcart Company (1856), as his counselor. The Richards brothers built a cabin, which became the first in a fort of log houses. Jesse Fox surveyed the site for the Territory of Utah. Ira Ames and George Snyder built a sawmill.
During an 1859 visit to the Cache Valley settlements, Orson Hyde, President of the Quorum of the Twelve Apostles, accompanied by Apostle Ezra Benson, on 19 December organized the Mendon Ward. Apostle Benson selected the Massachusetts town of his birth as the name of the new ward. On 19 February 1860 Andrew Shumway was ordained bishop under the hands of LDS Church President Brigham Young and Apostle Benson.
A pine log school/meeting house was erected in 1860. Gardner's Creek was dammed to irrigate the farms during a drought. A U.S. Post Office was established in the spring of 1861 with Willie as postmaster. Joel Ricks established a ferry across the Little Bear River, providing a direct route from Logan to Mendon. In 1863 Mendon settlers provided aid to the wounded soldiers who participated in the Bear River Massacre under the command of Colonel Patrick Connor. Other frontier incidents involved natives and wild bears. For instance, Henrietta Bird in 1863 used a flatiron and a poker to kill a bear that made the mistake of entering her kitchen. After one of Chief Pocatello's braves was killed in Mendon, a child was kidnapped. For protection, construction on a never-finished rock wall around Mendon was undertaken.
On 29 October 1863 county surveyor James Martineau drew up a plot of Mendon City, laid out into nine square blocks with a central square. Each block was divided into eight lots, each ten rods wide and twenty rods long, with six-rod-wide streets. In the spring the log houses were moved to the outer lots and orchards were planted. George Thurston and Kelsey Bird built a grist mill on Gardner's Creek. Construction was started on rock homes and on a 28-by-45-foot native rock church, designed by George Baker.
In 1869 commerce was stimulated by the establishment of a federal land office in Utah and the joining of the transcontinental railroad thirty-one miles west of Mendon. A ZCMI branch was organized in Mendon with Willie as general manager; and Albert Baker built a hotel with local rock. Henry Hughes began a long tenure as local bishop. On 12 February 1870 the Legislative Assembly passed an act incorporating Mendon City; the effective date was 1 April 1870. George Baker was elected first mayor.
Utah Northern Railroad started construction in 1871 on a roadbed over Collinston Hill into Mendon; the depot was on the town square. The town's population was 427. In 1873 the rock Mendon co-op building was erected. Apostle Erastus Snow organized a twenty-member United Order in Mendon; however, it lasted only a year. After 1889 Hyrum Richards operated the store. John Anderson opened another store in 1901.
A Presbyterian chapel school was erected in 1883 with William R. Campbell as pastor. However, most Mendonites were Mormons, and in the period from 1887 to 1890, because of their plural wives, a number of the men were sent to jail under the Edmunds-Tucker Act.
After 1872 Mendon went from a self-sufficient pioneer hamlet to an irrigated wheat farming area dependent upon external markets. Farming was central to the town's existence. After 1890 diversification of farming included the raising of alfalfa, sugar beets, dairy cows, and draft horses. In the twentieth century, mechanization and market farming altered the community's character, and Mendon became a mother community to new towns as many of its young people moved away to farms in southern Idaho.
Joseph Baker built a rock dance hall in Mendon in 1896, apparently the first in the valley. A new schoolhouse was constructed in 1899. In 1906-07, a railroad spur line linked Mendon and Hyrum. By 1907 Mendon was known for its thoroughbred horses, particularly of the draft breeds. The Forster Hotel was a favorite haven for weekend visitors to the Mendon horse races.
Following outbreaks of typhoid fever and diphtheria, voters bonded for a $10,000 culinary water system, which was completed in 1912. In 1913 construction began on a new LDS meetinghouse. Mendon students went to South Cache High School in Hyrum on the interurban electric railroad (which looped through Cache Valley all the way from Mendon to Hyrum and thence north to Richmond via Logan ). Electric interurban service began in 1914. A connecting line was run from Mendon to Brigham City. The railway was used to haul sugar beets to the refineries. Following peak production in 1920, local sugar beets fell victim to duty-free cane sugar imports, and the interurban railroad ceased operation in 1947.
The local May Day celebrations date back to 1874 and feature the selection of a queen and a dance of maidens around a maypole. Since World War II Mendon has increasingly become less of a farming village and more of a "bedroom" community for residents who commute to work in Logan or elsewhere.