Archaeological evidence indicates a human presence in the area as early as 7000 BCE at the Yumuktepe mound, 9 km to the northeast. The first known Luwian settlements and fortifications at Soli proper date the 15th century BCE, and the city was an active port from that time onwards. Soli may have functioned as the harbor city of Kizzuwatna, but this is disputed. The region was controlled by the Hittite Empire from the 14th-13th centuries BCE, and recovered Mycenaean bronzes and ceramics indicate trade with the Aegean.
The Bronze Age Collapse ended Hittite hegemony in Cilicia, and Soli may have suffered an attack from the Sea Peoples. This "destruction layer" is populated by burned and broken pottery and is followed by a hiatus in human occupation.
Achaean and Rhodian colonists reestablished a permanent human presence at Soli between 700 and 690 BCE, leaving behind geometric pottery characteristic of the Archaic period.
Cilicia became a vassal state to and satrapy of the Achaemenid Empire after the reign of Cyrus the Great, assisting the Persians in multiple military campaigns. Soli briefly allied itself with the Delian League, but otherwise prospered under Achaemenid hegemony, minting coins to the Persian standard until Alexander the Great drove the Persians out of Cilicia in 333 BCE. He imposed a fine of 200 talents on the city for favoring the Persians, imposed a democratic constitution, made a sacrifice to Asclepius and held honorary games. A year later, Alexander extracted three triremes from Soli and nearby Mallus to assist in his siege of Tyre.
After Alexander's death (323 BCE), Soli fell to the control of Ptolemy I Soter, and was attacked unsuccessfully by Demetrius I Poliorcetes. Cilicia traded hands between Alexander's successors until the end of the Fifth Syrian War (197 BCE), at which point Soli was held by the Seleucid Empire. Throughout the Hellenistic Period, the city gained considerable local autonomy, minting its own coinage and largely conducting its own affairs. Rhodes appealed to the Roman Senate to liberate Soli from the Seleucids on the grounds of their common heritage, but this case was dropped. Tigranes the Great of Armenia sacked Soli during the Seleucid Empire's collapse (83 BCE), and took the city's citizens to inhabit Tigranocerta, his newly founded capital.
In 67 BCE, the lex Gabinia was passed by the Roman Senate, endowing Pompeius Magnus (Pompey) with proconsular powers to combat piracy in the Eastern Mediterranean. After subduing the pirates, he resettled some surrendered pirates in the depopulated Soli, renaming it Pompeiopolis (not to be confused with the Pompeiopolis in nearby Paphlagonia, also founded around this time). The harbor was improved and expanded with Roman concrete, and new city walls, a theater and baths were built. The harbor was renovated again by 130 CE under the aegis of Antoninus Pius (though the project may have been begun by Hadrian), and the port city flourished under Roman rule.
After defeating Valerian at Edessa in spring of 260 CE, Sassanid King Shapur I invaded Cilicia and was defeated while sieging Soli-Pompeiopolis. The exact circumstances of the battle are disputed.
The Soli-Pompeiopolis became a bishopric sometime around 300 CE. In 525 CE, the city was leveled by a powerful earthquake and largely abandoned.