Claudius’ last wife was Agrippina the Younger. She was first married to (1st century AD) Gnaeus Domitius Ahenobarbus. From this marriage she gave birth to Lucius Domitius Ahenobarbus, who would become Roman Emperor Nero. Her husband died in January, 40. While still married, Agrippina participated openly in her brother Caligula's decadent court, where, according to some sources, at his instigation she prostituted herself in a palace. While it was generally agreed that Agrippina, as well as her sisters, had ongoing sexual relationships with their brother Caligula, incest was an oft-used criminal accusation against the aristocracy, because it was impossible to refute successfully. As Agrippina and her sister became more problematic for their brother, Caligula sent them into exile for a time, where it is said she was forced to dive for sponges to make a living. In January, 41, Agrippina had a second marriage to the affluent Gaius Sallustius Crispus Passienus. He died between 44 and 47, leaving his estate to Agrippina.

As a widow, Agrippina was courted by the freedman Pallas as a possible marriage match to her own uncle, Emperor Claudius, and became his favorite councilor, even granted the honor of being called Augusta (a title which no other queen had ever received). They were married on New Year's Day of 49, after the death of Claudius's first wife Messalina. Agrippina then proceeded to persuade Claudius to adopt her son, thereby placing Nero in the line of succession to the Imperial throne over Claudius's own son, Brittanicus. A true Imperial politician, Agrippina did not reject murder as a way to win her battles. Many ancient sources credited her with poisoning Claudius in 54 with a plate of poisoned mushrooms, hence enabling Nero to quickly take the throne as emperor.