Lucca was founded by the Etruscans, there are traces of a pre-existing Ligurian settlement, and became a Roman colony in 180 BC.

The rectangular grid of its historical centre preserves the Roman street plan, and the Piazza San Michele occupies the site of the ancient forum. Traces of the amphitheater can still be seen in the Piazza dell'Anfiteatro.

At the Lucca Conference, in 56 BC, Julius Caesar, Pompey, and Crassus reaffirmed their political alliance known as the First Triumvirate.

At one point, Lucca was plundered by Odoacer, the first Germanic King of Italy.
Lucca was an important city and fortress even in the 6th century, when Narses besieged it for several months in 553. Under the Lombards, it was the seat of a duke who minted his own coins. The Holy Face of Lucca (or Volto Santo), a major relic supposedly carved by Nicodemus, arrived in 742. During the 8th - 10th centuries Lucca was a center of Jewish life, the Jewish community being led by the Kalonymos family.

Lucca became prosperous through the silk trade that began in the 11th century, and came to rival the silks of Byzantium.

During the 10–11th centuries Lucca was the capital of the feudal margraviate of Tuscany, more or less independent but owing nominal allegiance to the Holy Roman Emperor.