It is notable as the birthplace of Pope Pius VI and Pope Pius VII, and once had Pope Pius VIII as bishop, and is therefore calls itself the "city of the three popes".
Cesena was originally an Umbrian town, then taken over by Romans in the 3rd century BC. It was destroyed in the wars between Marius and Sulla. Pliny mentions the wines of Cesena as among the best.
From 752 to 1861, it was a fief directly held by the pope. In 1377, Robert of Geneva, a legate of Pope Gregory XI (and later anti-Pope Clement VII) sacked the town, massacring many of the inhabitants. But during the period 1379-1465, it recovered and prospered under the rule of the Malatesta family, who built a castle overlooking the town. The Malatestiana Library in the castle is considered a fine example of a Renaissance library and holds many valuable manuscripts.
Cesena's industry centers on agriculture, handicrafts, and tourism.