On April 4, 1750 he married Ann Eilbeck who later passed away on March 9, 1773 after 23 years of marriage.

Mason was appointed treasurer of the Ohio Company in 1751 and served until he died. In 1758 he was appointed to represent Fairfax County in the Virginia House of Burgesses and served until 1761.

Thomas Jefferson said, (3) "George is a man of first order, of wisdom among those who acted on theatre of revolution, expensive mind, profound judgment, cogent in argument, learned in lore of our former constitution in earnest for the republican change on democratic principles. His education is neither flowing nor smooth, but his language is strong, manner most impressive, and strengthened by a dash of cynicism when provocation made it seasonable".

In 1759, George and his wife finished Gunston Hall, the plantation home on the Potomac River, and later moved in.

As a protest of the Stamp Act, in 1765, Mason wrote a letter to London Public Ledger opposing the act and signed it a "Virginia Planter".

In 1769, Mason drew up the nonimportion resolutions which were introduced by George Washington, a neighbor and lifelong friend. Five years later in July of 1774, Mason served on the Fairfax County Committee of Safety and oversaw formation of an independent militia company for Virginia, and on the 18th he wrote the series of 24 resolutions known as the "Fairfax Resolves", which advocated a congress of the colonies and urged a trade boycott against Britain.

A year later in 1775, George was chosen as a Fairfax County delegate to the Virginia Convention. In 1776, he prepared drafts of the first Declaration of Rights, which was the most advanced statement of the rights of a man up to that date. He also prepared drafts of the state constitution in the colonies. Then in June, the Virginia Declaration of Rights and the Virginia Constitution were written. Mason wrote most of the Virginia Constitution and this democratic document had great influence upon American political thought and institutions, and served largely as a model for the first ten amendments to the federal constitution.

George was a member of the Virginia Assembly from 1776 until 1778 and designed a seal for the commonwealth.

In 1780, George remarried to Sarah Brennt of Stafford County, Virginia, and the next year, because of poor health, Mason withdrew from the legislature.

In 1786, George was appointed to represent Virginia as a delegate to a Federal Convention. Here he contributed greatly to the formation of the Constitution but he however would not sign it and provided a list of objections to explain why. He made the first of his recorded 136 speeches, favored a total revision of the Articles of Confederation, argued for congress rather than the president having the power to declare war, wrote objections to the Constitution of Government on the back of a committee report and said he "would sooner chop off his right hand than put it to the Constitution as it now stands".

He also opposed sectional compromises relative to slavery, tariffs and slave trade, and he favored gradual emancipation of the slaves. He also objected to the extensive but vague powers given to Congress and joined Patrick Henry in opposing ratification in the 1778 Virginia Convention. Here he proposed a list of amendments, the substance of which was later included in the Bill of Rights. A little after this in 1787, he retired from active politics and spent time assisting his sons with business ventures.

In 1789 the drafting of the Declaration of Rights of Man took place which was strongly based on Mason's Virginia Declaration of Rights.

In March of 1790, Mason was appointed to fill a vacancy to the Virginia Senate but because of poor health decided not to serve.

George was ahead of his time in opposing slavery and rejecting the Constitutional compromise that perpetuated it. He was also a land owner, a near-neighbor of George Washington and help to found the town of Alexandria, Virginia.

Mason strongly objected the compromise that allowed the importation of slaves to go on until 1808. He was one of the only Southerners who opposed slavery and felt slaves should be educated and gradually freed. George Mason was dissatisfied that his fellow delegates didn't meet his concerns, so he refused to sign the Constitution.

Overall, Mason wrote many documents and inspired others to use his ideas to write many more.