In the War of Wrath that brought the First Age to an end, most of Morgoth's Orcs were destroyed, but some of his vast army escaped eastward across the Blue Mountains. Some of those crossed Eriador and found their way to the Misty Mountains, where they settled in caverns beneath the peaks. At first they were leaderless and wild, but Morgoth's lieutenant Sauron soon arose again in Middle-earth and took at least some control over them. By the end of the Second Age, Orcs of Mordor had come among them, and under their command the Orcs of the Mountains ambushed and killed Isildur after the War of the Last Alliance.

With Sauron's defeat in that war, the Orcs of the Misty Mountains again fell back to their wild ways. At least some bands had their own leaders, especially large Orcs like the Great Goblin, who were perhaps descendants of the Mordor-orcs sent to command them in the Second Age. After the fall of Khazad-dûm in III 1981, Orcs of the Misty Mountains entered and occupied its ruins. Long afterwards, Moria became the seat of an Orc-chieftain named Azog. It was Azog who slew King Thrór of the Longbeards, and so started the War of the Dwarves and Orcs, in which Azog himself was slain.

After that War, many of these Orcs fled from their mountain homes, while others lurked among the Misty Mountains, nursing a hatred of the Dwarves. In III 2941, a group of these Orcs captured a band of travelling Dwarves in the High Pass. Those Dwarves - led by Thrór's grandson Thorin - escaped, killing the Great Goblin in the process. So began a chain of events that led to Azog's son, Bolg, uniting the Orcs of the Misty Mountains and leading them east to fight the Battle of Five Armies. That battle ended in defeat for the Orcs, and left the Misty Mountains free of them for many years afterwards.

By the time of the War of the Ring, the Orcs of the Mountains had started to recover their numbers, at least sufficiently to reclaim Moria. As the War came on, they fell under the command of Sauron and Saruman. There were Orcs from the Misty Mountains, for example, in the party that captured Merry and Pippin at Parth Galen. Of their fate after the War, nothing is known, but legend says that the Longbeards eventually succeeded in recapturing Moria, so the power of the Orcs in the Misty Mountains must have waned considerably after the Third Age if they survived at all.