The following year Ebenezer Hanks, responding to a mission call to colonize the area, settled north of the Henrys, along the Fremont River, with several other families. A post office was established there in 1885, at which time the town was named Hanksville. By 1890 there were twenty families in the town, and in 1893 LDS Church records showed a population of more than 500 people living in the region. Many other small communities were established along the Fremont River--Giles, Mesa, Clifton, Blue Valley, Notom--but a series of disastrous floods in the 1890s and early 1900s drove most of the settlers away and today only Hanksville survives. South of the mountains were small communities at Hite and Halls Crossing, both being crossings of the Colorado River in Glen Canyon. Today Bullfrog, a recreational community servicing Lake Powell, flourishes on the southern end of the Henrys.

Cattlemen from Colorado moved their herds onto the northern end of the Henrys in the late 1870s, but the practice lasted only a few years before they moved on. By the 1890s, however, many ranches had been established in the Henrys themselves, and a number are still in operation. The first large herds of sheep were introduced into the Henrys around 1900, and by 1925 sheep had largely replaced cattle on the range. Shortly after World War I a large herd of goats was introduced; some of their descendants, since become feral, are said to still survive in the area. The large herds of sheep and cattle badly overgrazed the slopes of the Henrys, and the ranges have not recovered to the present day. Where there are cattle there are cattle rustlers, and the Henrys had their share of outlaws and other shady characters. The Outlaw Trail passed nearby, and one of the most used hideouts was the Robbers Roost country, just east of the Henrys. This area was the haunt of many desperadoes, including the Wild Bunch. Outlaws probably passed through or hid in the Henrys, and certainly hunted there, but most of their activities were elsewhere.