Powell began his public career deputy sheriff of Prince William County under his uncle Col. Henry Peyton.

He purchased 500 acres in newly formed Loudoun County and moved there in 1763, shortly after marrying his wife, Sally, whose planter father Burr Harrison owned a large estate further upstream along the Potomac River.

[6] He (or his son of the same name) owned 13 slaves in 1810, the year Powell died visiting a health spring in Pennsylvania.

[8] As relations with Great Britain worsened in the years before the American Revolutionary War, Powell served on the 15-member Loudoun County Committee of Safety in 1774.

[9] In either 1774 or 1775 he accepted a commission as major in a company of Loudoun County minutemen that traveled to southeastern Virginia, where they harassed Lord Dunmore's troops in Norfolk and Hampton and were ultimately incorporated into the Continental Army.

[11] However, health complications due to the harsh winter encampment at Valley Forge (which nearly caused him to lose an eye) led Powell to resign in 1778, although the Virginia General Assembly would later vote him a full share of land for his service.

Lt. William Powell III (1745–1807) served three years under Lt. Col. Daniel Morgan, and the youngest brother Lt. John Payton Powell (1760–1844) also served in Morgan's 11th Virginia Regiment (renamed the 7th Virginia Regiment in 1779), then received land and moved westward—first to Hardeman County, Tennessee and eventually died in Madison County, Alabama.

[14] Powell first won election to the Virginia House of Delegates in 1779, representing Loudoun County (part-time) alongside his cousin, veteran Francis Peyton.

[24] In the 1796 presidential election, Powell stood alone among Virginia's 21 electors in voting for John Adams over Thomas Jefferson.