The novel is set in the late 1620s, chiefly in France. It begins with a young man named D'Artagnan (most of the characters are known only by their surnames) who is traveling from his native Gascony to Paris with the hope of starting a military career. He is from a noble family, as opposed to the servant or bourgeois/trade/professional class, but is not wealthy. However he bears a letter of introduction to Monsieur de Tréville, captain of the Musketeers, that he believes will secure him a place in the King's Musketeers, an elite guard and military unit. At this time, there is a strong and sometimes violent rivalry between Treville and his musketeers, and the wily Cardinal Richelieu and his own set of guards. Richelieu is an influential adviser to King Louis but is always scheming to build his own power and influence.
Shortly after arriving in Paris, D'Artagnan meets three of the Musketeers: Athos, Porthos, and Aramis. After an initially tumultuous meeting, D'Artagnan earns the respect of the musketeers, and the four men become close friends. Through a connection via the wife of his landlord, Constance Bonacieux, D'Artagnan becomes aware of a potential scandal involving Queen Anne (the wife of King Louis) and the Duke of Buckingham, an English nobleman. Cardinal Richelieu concocts a plot, using his network of spies and allies, to attempt to embarrass the Queen by revealing her love for Buckingham. With the help of the musketeers, D'Artagnan foils the plot and saves the Queen's reputation.
However, D'Artagnan has now been dangerously drawn into a web of schemes and spying, and falls under the spell of Milady de Winter, one of the Cardinal's agents. When he learns that Milady is already in love with one of the Cardinal's allies, the Comte de Wardes, D'Artagnan tricks and betrays her. As a result, she becomes his sworn enemy.
D'Artagnan and the other musketeers now have to contend with military service due to a war France is fighting. Because of his love for Queen Anne, Buckingham is planning to send troops and supplies to support France's enemies, and Richelieu is desperate to ensure the French war efforts are not jeopardized. He sends Milady to assassinate Buckingham.
Learning of this plot, D'Artagnan and the musketeers act quickly, and are able to get word to Milady's brother, the Lord de Winter, who imprisons her once she arrives in England to carry out her mission. However, Milady seduces her jailer, Felton, and dispatches him to murder Buckingham on her behalf while she returns to England. The assassination is carried out before the allies of the musketeers can stop it, and upon her return to France, Milady also poisons and kills Constance as revenge against D'Artagnan. Once they track her down, the musketeers have Milady killed as punishment for these crimes, and for others spanning many years of her previous life.
Once the musketeers reunite with the Cardinal, he acknowledges their bravery and valor, and decides that the antagonism will stop. He even offers one of them a promotion, but since the three older men are hoping to step away from military service soon and take their lives in different directions, they decline. At the end of the novel, D'Artagnan becomes a lieutenant in the Musketeers.
