Mary Ann Evans was born in Nuneaton, Warwickshire, England. She was the second child of Robert Evans (1773–1849) and Christiana Evans (née Pearson, 1788–1836), the daughter of a local mill-owner. Mary Ann's name was sometimes shortened to Marian. Her full siblings were Christiana, known as Chrissey (1814–59), Isaac (1816–1890), and twin brothers who survived a few days in March 1821. She also had a half-brother, Robert (1802–64), and half-sister, Fanny (1805–82), from her father's previous marriage to Harriet Poynton (?1780–1809). Her father Robert Evans, of Welsh ancestry, was the manager of the Arbury Hall Estate for the Newdigate family in Warwickshire, and Mary Ann was born on the estate at South Farm. In early 1820 the family moved to a house named Griff House, between Nuneaton and Bedworth.

The Philosopher and critic George Henry Lewes (1817–78) met Evans in 1851, and by 1854 they had decided to live together. Lewes was already married to Agnes Jervis. They had an open marriage. In addition to the three children they had together, Agnes also had four children by Thornton Leigh Hunt. Because Lewes allowed himself to be falsely named as the father on the birth certificates of Jervis's illegitimate children, he was considered to be complicit in adultery, and therefore he was not legally able to divorce her. In July 1854, Lewes and Evans travelled to Weimar and Berlin together for the purpose of research. Before going to Germany, Evans continued her theological work with a translation of Feuerbach's The Essence of Christianity, and while abroad she wrote essays and worked on her translation of Baruch Spinoza's Ethics, which she completed in 1856, but which was not published in her lifetime.

Throughout her career, Eliot wrote with a politically astute pen. From Adam Bede to The Mill on the Floss and Silas Marner, Eliot presented the cases of social outsiders and small-town persecution. Felix Holt, the Radical and The Legend of Jubal were overtly political, and political crisis is at the heart of Middlemarch, in which she presents the stories of a number of inhabitants of a small English town on the eve of the Reform Bill of 1832; the novel is notable for its deep psychological insight and sophisticated character portraits. The roots of her realist philosophy can be found in her review of John Ruskin's Modern Painters in Westminster Review in 1856.

In 1836 her mother died and Evans (then 16) returned home to act as housekeeper, but she continued correspondence with her tutor Maria Lewis. When she was 21, her brother Isaac married and took over the family home, so Evans and her father moved to Foleshill near Coventry. The closeness to Coventry society brought new influences, most notably those of Charles and Cara Bray. Charles Bray had become rich as a ribbon manufacturer and had used his wealth in the building of schools and in other philanthropic causes. Evans, who had been struggling with religious doubts for some time, became intimate friends with the progressive, free-thinking Brays, whose "Rosehill" home was a haven for people who held and debated radical views. The people whom the young woman met at the Brays' house included Robert Owen, Herbert Spencer, Harriet Martineau, and Ralph Waldo Emerson. Through this society Evans was introduced to more liberal theologies and to Writers such as David Strauss and Ludwig Feuerbach, who cast doubt on the literal truth of Biblical stories. In fact, her first major literary work was an English translation of Strauss's The Life of Jesus (1846), which she completed after it had been left incomplete by another member of the "Rosehill Circle"; later she translated Feuerbach’s The Essence of Christianity (1854). As a product of their friendship, Bray published some of Evans's earliest writing, such as reviews, in his newspaper the Coventry Herald and Observer.

When Evans began to question her religious faith, her father threatened to throw her out of the house, but his threat was not carried out. Instead, she respectfully attended church and continued to keep house for him until his death in 1849, when she was 30. Five days after her father's funeral, she travelled to Switzerland with the Brays. She decided to stay on in Geneva alone, living first on the lake at Plongeon (near the present-day United Nations buildings) and then on the second floor of a house owned by her friends François and Juliet d'Albert Durade on the rue de Chanoines (now the rue de la Pelisserie). She commented happily that "one feels in a downy nest high up in a good old tree". Her stay is commemorated by a plaque on the building. While residing there, she read avidly and took long walks in the beautiful Swiss countryside, which was a great inspiration to her. François Durade painted her portrait there as well.

On her return to England the following year (1850), she moved to London with the intent of becoming a Writer, and she began referring to herself as Marian Evans. She stayed at the house of John Chapman, the radical publisher whom she had met earlier at Rose Hill and who had published her Strauss translation. Chapman had recently purchased the campaigning, left-wing journal The Westminster Review, and Evans became its assistant Editor in 1851. Although Chapman was officially the Editor, it was Evans who did most of the work of producing the journal, contributing many essays and reviews beginning with the January 1852 issue and continuing until the end of her employment at the Review in the first half of 1854.

While continuing to contribute pieces to the Westminster Review, Evans resolved to become a Novelist, and she set out a manifesto for herself in one of her last essays for the Review, "Silly Novels by Lady Novelists" (1856). The essay criticised the trivial and ridiculous plots of contemporary fiction by women. In other essays, she praised the realism of novels that were being written in Europe at the time, and it became clear in her subsequent fiction that she placed an emphasis on realistic storytelling. She also adopted a nom-de-plume, the one for which she would become known: George Eliot. This pen-name was said by some to be an homage to George Lewes. In addition to adopting his first name, the last name, Eliot, could possibly have been a code for "to L—I owe it".

In 1857, when she was 37, "The Sad Fortunes of the Reverend Amos Barton", the first of the Scenes of Clerical Life, was published in Blackwood's Magazine and, along with the other Scenes, it was well received (it was published in book form early in 1858). Her first complete novel, published in 1859, was Adam Bede; it was an instant success, but it prompted intense interest in who this new author might be. Scenes of Clerical Life was widely believed to have been written by a country parson or perhaps the wife of a parson. With the release of the incredibly popular Adam Bede, speculation increased, and there was even a pretender to the authorship, one Joseph Liggins. In the end, the real George Eliot stepped forward: Marian Evans Lewes admitted she was the author. The revelations about Eliot's private life surprised and shocked many of her admiring readers, but this did not affect her popularity as a Novelist. Eliot's relationship with Lewes afforded her the encouragement and stability she so badly needed to write fiction, and to ease her self-doubt, but it would be some time before they were accepted into polite society. Acceptance was finally confirmed in 1877 when they were introduced to Princess Louise, the daughter of Queen Victoria. The queen herself was an avid reader of all of George Eliot's novels and was so impressed with Adam Bede that she commissioned the Artist Edward Henry Corbould to paint scenes from the book.

After the success of Adam Bede, Eliot continued to write popular novels for the next fifteen years. Within a year of completing Adam Bede, she finished The Mill on the Floss, dedicating the manuscript: "To my beloved husband, George Henry Lewes, I give this MS. of my third book, written in the sixth year of our life together, at Holly Lodge, South Field, Wandsworth, and finished 21 March 1860."

Her last novel was Daniel Deronda, published in 1876, after which she and Lewes moved to Witley, Surrey. By this time Lewes's health was failing, and he died two years later, on 30 November 1878. Eliot spent the next two years editing Lewes's final work, Life and Mind, for publication, and she found solace and companionship with John Walter Cross, a Scottish commission agent whose mother had recently died.

On 16 May 1880 Eliot courted controversy once more by marrying John Cross, a man twenty years her junior, and again changing her name, this time to Mary Anne Cross. The legal marriage at least pleased her brother Isaac, who had broken off relations with her when she had begun to live with Lewes, but now sent congratulations. While the couple was honeymooning in Venice, Cross, in a fit of depression, jumped from the hotel balcony into the Grand Canal. He survived, and the newlyweds returned to England. They moved to a new house in Chelsea, but Eliot fell ill with a throat infection. This, coupled with the kidney disease with which she had been afflicted for several years, led to her death on 22 December 1880 at the age of 61.

Eliot was not buried in Westminster Abbey because of her denial of the Christian faith and her "irregular" though monogamous life with Lewes. She was buried in Highgate Cemetery (East), Highgate, London, in the area reserved for religious dissenters and agnostics, beside the love of her life, George Henry Lewes. The graves of Karl Marx and her friend Herbert Spencer are nearby. In 1980, on the centenary of her death, a memorial stone was established for her in the Poets' Corner.

She was at her most autobiographical in Looking Backwards, part of her final published work Impressions of Theophrastus Such. By the time of Daniel Deronda, Eliot's sales were falling off, and she had faded from public view to some degree. This was not helped by the posthumous biography written by her husband, which portrayed a wonderful, almost saintly, woman totally at odds with the scandalous life people knew she had led. In the 20th century she was championed by a new breed of critics, most notably by Virginia Woolf, who called Middlemarch "one of the few English novels written for grown-up people". In 1994, literary critic Harold Bloom placed Eliot among the most important Western Writers of all time. In a 2007 authors' poll by TIME, Middlemarch was voted the tenth greatest literary work ever written. In 2015, Writers from outside the UK voted it first among all British novels "by a landslide". The various film and television adaptations of Eliot's books have re-introduced her to the wider reading public.

The young Evans was obviously intelligent, a voracious reader. Because she was not considered physically beautiful, Evans was thus not thought to have much chance of marriage, and because of her intelligence, her father invested in an education not often afforded women. From ages five to nine, she boarded with her sister Chrissey at Miss Latham's school in Attleborough, from ages nine to thirteen at Mrs. Wallington's school in Nuneaton, and from ages thirteen to sixteen at Miss Franklin's school in Coventry. At Mrs. Wallington's school, she was taught by the evangelical Maria Lewis — to whom her earliest surviving letters are addressed. In the religious atmosphere of the Miss Franklin's school, Evans was exposed to a quiet, disciplined belief opposed to evangelicalism.

Working as a translator, Eliot was exposed to German texts of religious, social, and moral philosophy such as Friedrich Strauss’s Life of Jesus, Feuerbach’s The Essence of Christianity, and Spinoza’s Ethics. Elements from these works show up in her fiction, much of which is written with her trademark sense of agnostic humanism. She had taken particular notice of Feuerbach’s conception of Christianity, positing that our understanding of the nature of the Divine was to be found ultimately in the nature of humanity projected onto a Divine figure. An Example of this philosophy appeared in her novel Romola, in which Eliot’s protagonist displayed a “surprisingly modern readiness to interpret religious language in humanist or secular ethical terms.” Though Eliot herself was not religious, she had respect for religious tradition and its ability to maintain a sense of social order and morality. The religious elements in her fiction also owe much to her upbringing, with the experiences of Maggie Tulliver from The Mill on the Floss sharing many similarities with the young Mary Ann Evans. Eliot also faced a quandary similar to that of Silas Marner, whose alienation from the church simultaneously meant his alienation from society. Because Eliot retained a vestigial respect for religion, German Philosopher Friedrich Nietzsche excoriated her system of morality for figuring sin as a debt that can be expiated through suffering, which he demeaned as characteristic of "little moralistic females à la Eliot."