Stephen Meek was born in Washington County, Virginia, on July 4, 1807. In his autobiography he claims to be a relative of President James K. Polk. He was educated in the local public schools in Virginia before beginning work for William Sublette in 1827. He began working as a laborer for Sublette's Rocky Mountain Fur Company in St. Louis, Missouri. Soon, however, he became a trapper for a variety of companies.
Meek joined an expedition with Benjamin Bonneville in 1831 as a trapper, while Bonneville was exploring the Great Salt Lake. From 1833 to 1834 he traveled to California with Joseph R. Walker. Meek moved to Oregon in 1835 and began working at the Hudson's Bay Company's Fort Vancouver for John McLoughlin. This included trips to California with Tom McKay.
In 1841, Meek bought the first lot of the Oregon City, Oregon, townsite from John McLoughlin and helped to survey the land. He joined the American mountaineers that year for one year. The following year he served as a guide for a wagon train of pioneers to the Willamette Valley from Fort Laramie, and in 1845 led the ill-fated group that followed him from the Oregon Trail on the Meek Cutoff. That party split from the main party that included Joel Palmer and Sam Barlow at Fort Hall. In May 1845, he married Elizabeth Schoonover at St. Louis, Missouri, with whom he later had one son, George. The Meeks would reside at Linn City, Oregon, until 1848.
Meek would later spend time in the mines of the California Gold Rush before settling in Siskiyou County, California. In 1850, he briefly returned to Oregon, before returning to California continuing to mine until 1865. In 1865, Elizabeth died, and he returned to working as a guide and trapper. Stephen Meek died in Etna, California, on January 8, 1889, at the age of 81.