Sharp was born in Durham in 1735. He had eight older brothers and five younger sisters. Five of his brothers survived their infancy and by the time Sharp had reached his midteens the family funds set aside for their education had been all but depleted, so Sharp was educated at Durham School but mainly at home.

Sharp's apprenticeship ended in 1757, and both his parents died soon after. That same year he accepted a position as Clerk in the Ordnance Office at the Tower of London. This civil Service position allowed him plenty of free time to pursue his scholarly and intellectual pursuits.

A memorial to Sharp was erected in Westminster Abbey, and he features in carved bas-relief on the side of the Clarkson Memorial, a memorial to fellow-abolitionist Thomas Clarkson (1760–1846).

Sharp's brother william held a regular surgery for the local poor at his surgery at Mincing Lane, and one day in 1765 when Sharp was visiting, he met Jonathan Strong. Strong was a young black slave from Barbados who had been so badly beaten by his master, David Lisle, a Lawyer, that he had been cast out into the street as useless. Sharp and his brother tended to his injuries and had him admitted to Barts Hospital, where his injuries were so bad they necessitated a four-month stay. The Sharps paid for his treatment and, when he was fit enough, found him employment with a Quaker apothecary friend of theirs. In 1767, Lisle saw Strong in the street and had him kidnapped and sold to a planter called James Kerr for £30. Strong was able to get word to Sharp, and in a court attended by the Lord Mayor and the Coroner of London, Lisle and Kerr were denied possession of Strong. They instituted a court action against Sharp claiming £200 damages for taking their property, and Lisle challenged Sharp to a duel—Sharp told Lisle that he could expect satisfaction from the law.

In 1769 Sharp published A Representation of the Injustice and Dangerous Tendency of Tolerating Slavery ..., the first tract in England attacking slavery. Sharp's work attracted the attention of James Oglethorpe, who had long been concerned with slavery as a moral issue. The two men remained close until Oglethorpe's death in 1785.

Calling on his now-formidable knowledge of the law regarding individual liberty, Sharp briefed Somerset's lawyers. Mansfield's deliberate procrastination stretched Somerset's Case over six hearings from January to May, and he finally delivered his judgment on 22 June 1772. It was a clear victory for Somerset, Sharp and the lawyers who acted for Somerset. Mansfield acknowledged that English law did not allow slavery, and only a new Act of Parliament ("positive law") could bring it into legality. However, the verdict in the case is often misunderstood to mean the end of slavery in England. It was no such thing: it dealt only with the question of the forcible sending of someone overseas into bondage; a slave becomes free the moment he sets foot on English territory. It was one of the most significant achievements in the campaign to abolish slavery throughout the world, more for its effect than for its actual legal weight.

Sharp ardently sympathized with the revolt of the American colonists. He believed in peace in America, but he also believed they were entitled to "Equitable Representation", an idea repeated in the famous phrase "No taxation without representation". When he realised his job in the Ordnance Office meant sending equipment to British forces fighting the colonists, he took leave of absence. As the war continued, he wrote to his employers "I cannot return to my ordnance duty whilst a bloody war is carried on, unjustly, against my fellow-subjects." Eventually in 1776 he resigned, never to have paid employment again and supported willingly by his brothers, who were happy to see him dedicate his time to his various causes.

One of Granville's letters written in 1778 (published in 1798), propounded what has come to be known as The Granville Sharp Rule (in actuality only the first of six principles that Sharp articulated involving the Greek article):

Although no reliable figures exist, it is thought that in the early 1780s there were around 15,000 black people in Britain, most of them without employment. Ideas were formulated for a settlement in Africa where they could return "home". Henry Smeathman, a plant collector and entomologist who had visited Sierra Leone, propounded to the Committee for the Relief of the Black Poor that the country would be an excellent location. Worried black people came to see Sharp, concerned that they might be re-enslaved in such a place.

In 1781 the crew of the over-capacity slaver ship Zong massacred an estimated 132 slaves by tossing them overboard; an additional ten slaves threw themselves overboard in defiance or despair and over sixty people had perished through neglect, injuries, disease and overcrowding.

Sharp was visited on 19 March 1783 by Olaudah Equiano, a famous freed slave and later to be the author of a successful autobiography, who told him of the horrific events aboard the Zong. Sharp immediately became involved in the court case, facing his old adversary over slave trade matters, the Solicitor General for England and Wales, Mr. John Lee. Lee notoriously declared that "the case was the same as if assets had been thrown overboard", and that a master could drown slaves without "a surmise of impropriety".

Sharp also advocated parliamentary reform and the legislative independence of Ireland, and agitated against the impressment of sailors for the Navy. It was through his efforts that bishops for the United States of America were consecrated by the Archbishop of Canterbury in 1787. He also argued for the reform of Parliament based on Magna Carta and to back this up he devised the doctrine of accumulative authority. This doctrine stated that because almost innumerable parliaments had approved Magna Carta it would take the same number of Parliaments to repeal it. Like many others, Sharp accepted the supremacy of Parliament as an institution, but did not believe that this power was without restraint, and thought that Parliament could not repeal Magna Carta.

Through The Society for Effecting the Abolition of the Slave Trade, in 1790 Granville came into contact with Thomas Peters, a former American slave who fought with the British during revolution in return for freedom. Sharp was instrumental in helping Peters to establish Freetown, Sierra Leone. Sharp is considered to be one of the founders of Sierra Leone alongside Thomas Peters and the Clarkson brothers (Thomas Clarkson and John Clarkson).

When Sharp heard that the Act of Abolition had at last been passed by both Houses of Parliament and given Royal Assent on 25 March 1807, he fell to his knees and offered a prayer of thanksgiving. He was now 71, and had outlived almost all of the allies and opponents of his early campaigns. He was regarded as the grand old man of the abolition struggle, and although a driving force in its early days, his place had later been taken by others such as Thomas Clarkson, william Wilberforce and the Clapham Sect. Sharp, however, did not see the final abolition as he died on 6 July 1813.

"Here by the Remains of the Brother and Sister whom he tenderly loved lie those of GRANVILLE SHARP Esqr. at the age of 79 this venerable Philanthropist terminated his Career of almost unparalleled activity and usefulness July 6th 1813 Leaving behind him a name That will be Cherished with Affection and Gratitude as long as any homage shall be paid to those principles of JUSTICE HUMANITY and RELIGION which for nearly half a Century He promoted by his Exertions and adorned by his Example"

In 2007, Sharp's tomb in the graveyard of All Saints' Church, Fulham was also restored to coincide with the anniversary. In recognition of Sharp's historical importance and preparation for the anniversary, the tomb was listed as Grade II on 16 March 2007, only three months after the application was made to English Heritage and the Department of Culture, Media and Sport. The tomb was restored in June 2007 and a ceremony to mark the completion of the work was held in the church, attended by many notable figures including Professor Simon Schama. Speaking at the Service, Schama said that "Sharp's great contribution was to 'lower the threshold of shame' in society."

However, just because Wallace exaggerates Winstanley's concession does not mean that he has no evidence to refute Winstanley. Wallace argues that, for various reasons, the only two passages from Granville's eight that truly follow Sharp's rule (for textual reasons, among others) are Titus 2:13 and 2 Peter 1:1. Wallace interacts in depth with Winstanley's critiques of Sharp and shows from grammatical, textual, linguistic, and Patristic evidence that Sharp's rule is truly valid across Classical, Biblical, Papyrological, and Patristic Greek – with some slight modification to the rules. Here is how Wallace restates the issue:

For a full discussion of Sharp's Rule and its application to passages in the New Testament which teach the deity of Christ, see the series "The Greek Article and the Doctrine of Christ's Deity," by Clifford Kuehne. This series appeared in several issues of the Journal of Theology of the Church of the Lutheran Confession, and it is available for reading at the following web site: http://jot.clclutheran.org/2017/02/25/christs-deity/ This series also discusses the application of Colwell's Rule to John 1:1.

This rule, if true, has a profound bearing on Unitarian doctrine, which led to a ‘celebrated controversy’, in which many leading divines took part, including Christopher Wordsworth.

But Wallace claims that this rule is often too broadly applied. “Sharp’s rule Number 1” does not always work with plural forms of personal titles. Instead, a phrase that follows the form article-noun-“and”-noun, when the nouns involved are plurals, can involve two entirely distinct groups, two overlapping groups, two groups of which is one a subset of the other, or two identical groups. In other words, the rule is of very specific and limited application.