Rome grew quickly in the years that followed thanks to its location along the Tiber River which carried traders from the north and south. Early on, Roma was dominated by the Etruscan peoples from the north (around current-day Tuscany). In 509 BC Rome finally gained independence and declared itself a Republic. Led by a Senate comprised of Rome's wealthiest citizens, the new Republic built temples to their gods modeled on the Greek tradition and began Rome's conquest of the Italian peninsula. The Punic Wars against Carthage in the 3rd Century established Rome as the dominant ruler of the entire Mediterranean, to which Rome referred to as "Our Private Sea."

As Rome grew rich, infighting began in the Senate, allowing Julius Caesar to cease power and declare himself dictator for life. Though beloved by the people, Caesar was not popular in the Senate and a group of 23 senators led by Marcus Brutus and Gaius Cassius conspired to plunge their knives into Caesar. On March 15, 44 BC, Caesar's wife Calpurnia begged him not to go to the Senate because she had had a dream that he lay dead in her arms. He went anyway and was attacked after Tillius Cimber gave the signal by tearing open Caesar's robe. Caesar fought back valiantly and almost escaped until he recognized his friend and possible illegitimate son Brutus among the assassins, at which point Caesar uttered his famous last words "et tu Brutus?"

After Julius, the line of Caesar's in Rome continued for another 300 years during a time of relative peace and prosperity known as Pax Romana.

The greatest tragedy during that time occurred in 64 A.D. under the reign of Emperor Nero, when Rome burned to the ground. The Great Fire of Rome began, most likely, in one of the temples in the Roman Forum and spread quickly through the city.