Livingston was born in Clermont, Columbia County, New York. He was the youngest son of Robert R. Livingston, the brother of Robert Livingston (1746-1813), grandson of Robert Livingston (1688-1775), and great-grandson of Robert Livingston the Elder (1654 - 1728). He was also brothers-in-law with John Armstrong, Jr. and Morgan Lewis (along with many other notable relations from the extended Livingston family).

Edward Livingston graduated from Princeton University in 1781, was admitted to the bar in 1785, and began to practice law in New York City, rapidly rising to distinction. From 1795 to 1801 he was a Republican U.S. Representative in the United States Congress from the state of New York, where he was one of the leaders of the opposition to Jay's Treaty, and introduced the resolution calling upon President George Washington to furnish Congress with the details of the negotiations of the peace treaty with Great Britain, which the President refused to share. At the close of Washington’s administration he voted with Andrew Jackson and other radicals against the address to the president.

Livingston was a prominent opponent of the Alien and Sedition Laws, introduced legislation on behalf of American seamen, and in 1800 attacked the president for permitting the extradition to the British government of Jonathan Robbins, who had committed murder on an English frigate and then escaped to South Carolina and falsely claimed to be an American citizen. In the debate on this question Livingston was opposed by John Marshall. In 1801 Livingston was appointed U.S. district attorney for the state of New York, and while retaining that position was in the same year appointed mayor of New York City. When, in the summer of 1803, the city was visited with yellow fever, Livingston displayed courage and energy in his endeavours to prevent the spread of the disease and relieve distress. He suffered a violent attack of fever, during which the people gave many proofs of their attachment to him. On his recovery he found his private affairs in some confusion, and he was at the same time deeply indebted to the government for public funds which had been lost through the mismanagement or dishonesty of a confidential clerk, and for which he was responsible as district-attorney. He at once surrendered all his property, resigned his two offices in 1803, and moved early in 1804 to Louisiana. He soon acquired a large law practice in New Orleans, and in 1826 repaid the government in full, including the interest, which at that time amounted to more than the original principal.

Almost immediately upon his arrival in Louisiana, where the legal system had previously been based on Roman, French and Spanish law, and where trial by jury and other peculiarities of English common law were now first introduced, he was appointed by the legislature to prepare a provisional code of judicial procedure, which (in the form of an act passed in April 1805) was continued in force from 1805 to 1825. In 1807, after conducting a successful suit on behalf of a client’s title to a part of the batture or alluvial land near New Orleans, Livingston attempted to improve part of this land (which he had received as his fee) in the Batture, Ste Hilarie. Great popular excitement was aroused against him; his workmen were mobbed; and Governor William C. C. Claiborne, when appealed to for protection, referred the question to the Federal government. It has been alleged that Livingston’s case was damaged by President Thomas Jefferson, who believed that Livingston had favoured Aaron Burr in the presidential election of 1800, and that he had afterwards been a party to Burr’s schemes. Jefferson made it impossible for Livingston to secure his title since by asserting the claim that such battures were the property of the Federal government, Livingston's title obtained from the Territorial Court notwithstanding. In response, Livingston filed a civil lawsuit against Jefferson in 1810. After the case was dismissed on 5 December, 1811 by Chief Justice John Marshall due to lack of jurisdiction (see Dumas Malone's biography "Jefferson and His Time - Volume 6, The Sage of Monticello - Chapter 5, The Batture Controversy"), nonetheless, Jefferson in 1812 completed and published a pamphlet originally intended “for the use of counsel” in the case against Livingston, to which Livingston published a reply. During the war with England from 1812 to 1815 (see: War of 1812) Livingston was active in rousing the mixed population of New Orleans to resistance. He used his influence to secure amnesty for Jean Lafitte and his followers upon their offer to fight for the city, and in 1814 - 1815 acted as adviser and volunteer aide-de- camp to General Andrew Jackson, who was his personal friend. In 1821, by appointment of the legislature, of which he had become a member in the preceding year, Livingston began the preparation of a new code of criminal law and procedure, afterwards known in Europe and America as the Livingston Code. It was prepared in both French and English, as was required by the necessities of practice in Louisiana, and actually consisted of four sections: crimes and punishments, procedure, evidence in criminal cases, reform and prison discipline. Though substantially completed in 1824, when it was accidentally burned, and again in 1826, it was not printed entire until 1833. It was never adopted by the state. It was at once reprinted in England, France and Germany, attracting wide praise by its remarkable simplicity and vigour, and especially by reason of its philanthropic provisions in the code of reform and prison discipline, which noticeably influenced the penal legislation of various countries. In referring to this code, Sir Henry Maine spoke of Livingston as “the first legal genius of modern times” (Cambridge Essays, 1856, p.17). The spirit of Livingston’s code was remedial rather than vindictive; it provided for the abolition of capital punishment and the making of penitentiary labour not a punishment forced on the prisoner, but a matter of his choice and a reward for good behaviour, bringing with it better accommodations. His Code of Reform and Prison Discipline was adopted the government of the United States of Central America under liberal president Francisco Morazán. Livingston was the leading member of a commission appointed to prepare a new civil code, which for the most part the legislature adopted in 1825, and the most important chapters of which, including all those on contract, were prepared by Livingston alone.

Livingston was again a representative in Congress during preliminary work in the preparation of a new civil code, done by James Brown and Moreau Lislet, who in 1808 reported a "Digest of the Civil Laws now in force in the Territory of Orleans with Alterations and Amendments adapted to the present Form Of Government”.

Livingston served as a U.S. Representative from Louisiana from 1823 - 1829, a U.S. Senator in 1829 - 1831, and for two years (1831 - 1833) United States Secretary of State under President Jackson. In this last position he was one of the most trusted advisers of the president, for whom he prepared a number of state papers, the most important being the famous anti-nullification proclamation of the 10th of December 1832.

From 1833 to 1835 Livingston was minister plenipotentiary to France, charged with procuring the fulfilment by the French government of the treaty negotiated by W. C. Rives in 1831, by which France had bound herself to pay an indemnity of twenty-five millions of francs for French spoliations of American shipping chiefly under the Berlin and Milan decrees, and the United States in turn agreed to pay to France 1,500,000 francs in satisfaction of French claims. Livingston's negotiations were conducted with excellent judgment, but the French Chamber of Deputies refused to make an appropriation to pay the first instalment due under the treaty in 1833, relations between the two governments became strained, and Livingston was finally instructed to close the legation and return to America.

Edward Livingston died at Montgomery Place, Rhinebeck, Dutchess County, New York, an estate left him by his sister, to which he had removed in 1831.

Livingston was twice married. His first wife, Liviary McEvers, whom he married on the 10 April 1788, died on the March 13, 1801. In June 1805 he married Madame Louise Moreau de Lassy or D'Avezac, a widow 19 years of age, whose maiden name was Davezac de Castera, and who was a refugee in New Orleans from the revolution in Santo Domingo. She was a woman of extraordinary beauty and intellect, and is said to have greatly influenced her husband's public career.