After a short period of study at Trinity Hall, Cambridge, he spent some time abroad, mainly in Paris. He was a great admirer of French manners, culture, and taste. He succeeded to the earldom in 1726 and became ambassador to Holland in 1728. His illegitimate son, Philip Stanhope, the recipient of the letters, was born there in 1732. Returning to England in the same year, Chesterfield took up a parliamentary career for the next decade as a strong opponent of Sir Robert Walpole. In spite of his connection by marriage to the king, he lost favour at court until he demonstrated his abilities as a statesman in his short term (August 1745–April 1746) as lord lieutenant of Ireland. After a term as secretary of state (1746–48), he gradually retired from public life because of increasing deafness, though he was largely responsible for Britain's decision to adopt the Gregorian calendar in 1752.

Chesterfield's winning manners, urbanity, and wit were praised by many of his leading contemporaries, and he was on familiar terms with Alexander Pope, John Gay, and Voltaire. He was the patron of many struggling authors but had unfortunate relations with one of them, Samuel Johnson (Johnson, Samuel), who condemned him in a famous letter (1755) attacking patrons. Johnson further damaged Chesterfield's reputation when he described the Letters as teaching “the morals of a whore, and the manners of a dancing master.” Dickens later caricatured him as Sir John Chester in Barnaby Rudge (1841). The opinion of these two more popular writers—both of whom epitomized middle-class morality—has contributed to Chesterfield's image as a cynical man of the world and a courtier. Careful readers of Chesterfield's letters, which were not written for publication, consider this an injustice. The strongest charge against his philosophy is that it leads to concentration on worldly ends. But within this limitation his advice is shrewd and presented with wit and elegance. Ironically, Chesterfield's painstaking advice seems to have fallen on deaf ears: his son was described by contemporaries as “loutish,” and his godson was described by Fanny Burney as having “as little good breeding as any man I ever met.”

Chesterfield left many other letters that are models of wit and charm, especially those written to the diplomat Solomon Dayrolles, a lifelong friend who was with him at his deathbed.