Rameau's early years are particularly obscure. He was born on 25 September 1683 in Dijon, and baptised the same day. His father, Jean, worked as an organist in several churches around Dijon, and his mother, Claudine Demartinécourt, was the daughter of a notary. The couple had eleven children (five girls and six boys), of whom Jean-Philippe was the seventh.

Rameau's three collections appeared in 1706, 1724 and 1726 or 1727, respectively. After this, he only composed a single piece for the harpsichord: "La Dauphine" (1747). Other works, such as "Les petits marteaux," have been doubtfully attributed to him.

In 1709, he moved back to Dijon to take over his father's job as organist in the main church. The contract was for six years, but Rameau left before then and took up similar posts in Lyon and Clermont. During this period, he composed motets for church performance as well as secular cantatas.

Little is known about Rameau's early years, and it was not until the 1720s that he won fame as a major theorist of music with his Treatise on Harmony (1722) and also in the following years as a Composer of masterpieces for the harpsichord, which circulated throughout Europe. He was almost 50 before he embarked on the operatic career on which his reputation chiefly rests today. His debut, Hippolyte et Aricie (1733), caused a great stir and was fiercely attacked by the supporters of Lully's style of music for its revolutionary use of harmony. Nevertheless, Rameau's pre-eminence in the field of French opera was soon acknowledged, and he was later attacked as an "establishment" Composer by those who favoured Italian opera during the controversy known as the Querelle des Bouffons in the 1750s. Rameau's music had gone out of fashion by the end of the 18th century, and it was not until the 20th that serious efforts were made to revive it. Today, he enjoys renewed appreciation with performances and recordings of his music ever more frequent.

Rameau's 1722 Treatise on Harmony initiated a revolution in music theory. Rameau posited the discovery of the "fundamental law" or what he referred to as the "fundamental bass" of all Western music. Heavily influenced by new Cartesian modes of thought and analysis, Rameau's methodology incorporated mathematics, commentary, analysis and a didacticism that was specifically intended to Illuminate, scientifically, the structure and principles of music. With careful deductive reasoning, he attempted to derive universal harmonic principles from natural causes. Previous treatises on harmony had been purely practical; Rameau embraced the new philosophical rationalism, quickly rising to prominence in France as the "Isaac Newton of Music." His fame subsequently spread throughout all Europe, and his Treatise became the definitive authority on music theory, forming the foundation for instruction in western music that persists to this day.

Rameau took his first tentative steps into composing stage music when the Writer Alexis Piron asked him to provide songs for his popular comic plays written for the Paris Fairs. Four collaborations followed, beginning with L'endriague in 1723; none of the music has survived.

Rameau's musical works may be divided into four distinct groups, which differ greatly in importance: a few cantatas; a few motets for large chorus; some pieces for solo harpsichord or harpsichord accompanied by other instruments; and, finally, his works for the stage, to which he dedicated the last thirty years of his career almost exclusively. Like most of his contemporaries, Rameau often reused melodies that had been particularly successful, but never without meticulously adapting them; they are not simple transcriptions. Besides, no borrowings have been found from other composers, although his earliest works show the influence of other music. Rameau's reworkings of his own material are numerous; e.g., in Les Fêtes d'Hébé, we find L'Entretien des Muses, the Musette, and the Tambourin, taken from the 1724 book of harpsichord pieces, as well as an aria from the cantata Le Berger Fidèle.

On 25 February 1726 Rameau married the 19-year-old Marie-Louise Mangot, who came from a musical family from Lyon and was a good singer and instrumentalist. The couple would have four children, two boys and two girls, and the marriage is said to have been a happy one.

During the first part of his operatic career (1733–1739), Rameau wrote his great masterpieces destined for the Académie royale de musique: three tragédies en musique and two opéra-ballets that still form the core of his repertoire. After the interval of 1740 to 1744, he became the official court musician, and for the most part, composed pieces intended to entertain, with plenty of dance music emphasising sensuality and an idealised pastoral atmosphere. In his last years, Rameau returned to a renewed version of his early style in Les Paladins and Les Boréades.

Not one of his librettists managed to produce a libretto on the same artistic level as Rameau's music: the plots were often overly complex or unconvincing. But this was standard for the genre, and is probably part of its charm. The versification, too, was mediocre, and Rameau often had to have the libretto modified and rewrite the music after the premiere because of the ensuing criticism. This is why we have two versions of Castor et Pollux (1737 and 1754) and three of Dardanus (1739, 1744, and 1760).

During his semiretirement in the years 1740 to 1744, he wrote the Pièces de clavecin en concert (1741), which some musicologists consider the pinnacle of French Baroque chamber music. Adopting a formula successfully employed by Mondonville a few years earlier, these pieces differ from trio sonatas in that the harpsichord is not simply there as basso continuo to accompany other instruments (the violin, flute or viol) playing the melody but has an equal part in the "concert" with them. Rameau also claimed that the pieces would be equally satisfying as solo harpsichord works—although this statement is far from convincing, since the Composer took the trouble to transcribe five of them himself—those where the lack of other instruments would show the least.

The year 1745 was a watershed in Rameau's career. He received several commissions from the court for works to celebrate the French victory at the Battle of Fontenoy and the marriage of the Dauphin to Infanta Maria Teresa Rafaela of Spain. Rameau produced his most important comic opera, Platée, as well as two collaborations with Voltaire: the opéra-ballet Le temple de la gloire and the comédie-ballet La princesse de Navarre. They gained Rameau official recognition; he was granted the title "Compositeur du Cabinet du Roi" and given a substantial pension. 1745 also saw the beginning of the bitter enmity between Rameau and Jean-Jacques Rousseau. Though best known today as a thinker, Rousseau had ambitions to be a Composer. He had written an opera, Les muses galantes (inspired by Rameau's Indes galantes), but Rameau was unimpressed by this musical tribute. At the end of 1745, Voltaire and Rameau, who were busy on other works, commissioned Rousseau to turn La Princesse de Navarre into a new opera, with linking recitative, called Les fêtes de Ramire. Rousseau then claimed the two had stolen the credit for the words and music he had contributed, though musicologists have been able to identify almost nothing of the piece as Rousseau's work. Nevertheless, the embittered Rousseau nursed a grudge against Rameau for the rest of his life.

Unlike Lully, who collaborated with Philippe Quinault on almost all his operas, Rameau rarely worked with the same librettist twice. He was highly demanding and bad-tempered, unable to maintain longstanding partnerships with his librettists, with the exception of Louis de Cahusac, who collaborated with him on several operas, including Les fêtes de l'Hymen et de l'Amour (1747), Zaïs (1748), Naïs (1749), Zoroastre (1749; revised 1756), La naissance d'Osiris (1754), and Anacréon (the first of Rameau's operas by that name, 1754). He is also credited with writing the libretto of Rameau's final work, Les Boréades (c. 1763).

His Zoroastre was first performed in 1749. According to one of Rameau's admirers, Cuthbert Girdlestone, this opera has a distinctive place in his works: "The profane passions of hatred and jealousy are rendered more intensely [than in his other works] and with a strong sense of reality."

His enemies exaggerated his faults; e.g. his supposed miserliness. In fact, it seems that his thriftiness was the result of long years spent in obscurity (when his income was uncertain and scanty) rather than part of his character, because he could also be generous. We know that he helped his nephew Jean-François when he came to Paris and also helped establish the career of Claude-Bénigne Balbastre in the capital. Furthermore, he gave his daughter Marie-Louise a considerable dowry when she became a Visitandine nun in 1750, and he paid a pension to one of his sisters when she became ill. Financial security came late to him, following the success of his stage works and the grant of a royal pension (a few months before his death, he was also ennobled and made a knight of the Ordre de Saint-Michel). But he did not change his way of life, keeping his worn-out clothes, his single pair of shoes, and his old furniture. After his death, it was discovered that he only possessed one dilapidated single-keyboard harpsichord in his rooms in Rue des Bons-Enfants, yet he also had a bag containing 1691 gold louis.

Rousseau was a major participant in the second great quarrel that erupted over Rameau's work, the so-called Querelle des Bouffons of 1752–54, which pitted French tragédie en musique against Italian opera buffa. This time, Rameau was accused of being out of date and his music too complicated in comparison with the simplicity and "naturalness" of a work like Pergolesi's La serva padrona. In the mid-1750s, Rameau criticised Rousseau's contributions to the musical articles in the Encyclopédie, which led to a quarrel with the leading philosophes d'Alembert and Diderot. As a result, Rameau became a character in Diderot's then-unpublished dialogue, Le neveu de Rameau (Rameau's Nephew).

In 1753, La Pouplinière took a scheming musician, Jeanne-Thérèse Goermans, as his mistress. The daughter of harpsichord maker Jacques Goermans, she went by the name of Madame de Saint-Aubin, and her opportunistic husband pushed her into the arms of the rich financier. She had La Pouplinière engage the services of the Bohemian Composer Johann Stamitz, who succeeded Rameau after a breach developed between Rameau and his patron; however, by then, Rameau no longer needed La Pouplinière's financial support and protection.

By the end of his life, Rameau's music had come under attack in France from theorists who favoured Italian Models. However, foreign composers working in the Italian tradition were increasingly looking towards Rameau as a way of reforming their own leading operatic genre, opera seria. Tommaso Traetta produced two operas setting translations of Rameau libretti that show the French composer's influence, Ippolito ed Aricia (1759) and I Tintaridi (based on Castor et Pollux, 1760). Traetta had been advised by Count Francesco Algarotti, a leading proponent of reform according to French models; Algarotti was a major influence on the most important "reformist" Composer, Christoph Willibald Gluck. Gluck's three Italian reform operas of the 1760s—Orfeo ed Euridice, Alceste, and Paride ed Elena—reveal a knowledge of Rameau's works. For instance, both Orfeo and the 1737 version of Castor et Pollux open with the funeral of one of the leading characters who later comes back to life. Many of the operatic reforms advocated in the preface to Gluck's Alceste were already present in Rameau's works. Rameau had used accompanied recitatives, and the overtures in his later operas reflected the action to come, so when Gluck arrived in Paris in 1774 to produce a series of six French operas, he could be seen as continuing in the tradition of Rameau. Nevertheless, while Gluck's popularity survived the French Revolution, Rameau's did not. By the end of the 18th century, his operas had vanished from the repertoire.

Rameau composed prolifically in the late 1740s and early 1750s. After that, his rate of productivity dropped off, probably due to old age and ill health, although he was still able to write another comic opera, Les Paladins, in 1760. This was due to be followed by a final tragédie en musique, Les Boréades; but for unknown reasons, the opera was never produced and had to wait until the late 20th century for a proper staging. Rameau died on 12 September 1764 after suffering from a fever, thirteen days before his 81st birthday. At his bedside, he objected to a song sung. His last words were, "What the devil do you mean to sing to me, priest? You are out of tune." He was buried in the church of St. Eustache, Paris on the same day of his death. Although a bronze bust and red marble tombstone were erected in his memory there by the Société de la Compositeurs de Musique in 1883, the exact site of his burial remains unknown to this day.

For most of the 19th century, Rameau's music remained unplayed, known only by reputation. Hector Berlioz investigated Castor et Pollux and particularly admired the aria "Tristes apprêts," but "whereas the modern listener readily perceives the Common ground with Berlioz' music, he himself was more conscious of the gap which separated them." French humiliation in the Franco-Prussian War brought about a change in Rameau's fortunes. As Rameau biographer J. Malignon wrote, "...the German victory over France in 1870–71 was the grand occasion for digging up great heroes from the French past. Rameau, like so many others, was flung into the enemy's face to bolster our courage and our faith in the national destiny of France." In 1894, Composer Vincent d'Indy founded the Schola Cantorum to promote French national music; the society put on several revivals of works by Rameau. Among the audience was Claude Debussy, who especially cherished Castor et Pollux, revived in 1903: "Gluck's genius was deeply rooted in Rameau's works... a detailed comparison allows us to affirm that Gluck could replace Rameau on the French stage only by assimilating the latter's beautiful works and making them his own." Camille Saint-Saëns (by editing and publishing the Pièces in 1895) and Paul Dukas were two other important French Musicians who gave practical championship to Rameau's music in their day, but interest in Rameau petered out again, and it was not until the late 20th century that a serious effort was made to revive his works. Over half of Rameau's operas have now been recorded, in particular by conductors such as John Eliot Gardiner, william Christie, and Marc Minkowski.

Along with François Couperin, Rameau is one of the two masters of the French school of harpsichord music in the 18th century. Both composers made a decisive break with the style of the first generation of harpsichordists, who confined their compositions to the relatively fixed mould of the classical suite. This reached its apogee in the first decade of the 18th century with successive collections of pieces by Louis Marchand, Gaspard Le Roux, Louis-Nicolas Clérambault, Jean-François Dandrieu, Elisabeth Jacquet de la Guerre, Charles Dieupart, and Nicolas Siret.