The Mekong Delta was likely inhabited long since prehistory; the empire of Funan and later Chenla maintained a presence in the Mekong Delta for centuries. Archaeological discoveries at Oc Eo and other Funan sites show that the area was an important part of the Funan Kingdom, bustling with trading ports and canals as early as in the first century CE and extensive human settlement in the region may have gone back as far as the 4th century BCE.
The region was known as Khmer Krom (lower Khmer, or lower Cambodia) to the Khmer Empire, which likely maintained settlements there centuries before its rise in the 11th and 12th centuries. The kingdom of Champa, though mainly based along the coast of the South China Sea, is known to have expanded west into the Mekong Delta, seizing control of Prey Nokor (the precursor to modern-day Ho Chi Minh City) by the end of the 13th century.
Beginning in the 1620s, Khmer king Chey Chettha II (1618–1628) allowed the Vietnamese to settle in the area, and to set up a custom house at Prey Nokor, which they colloquially referred to as Sài Gòn. The increasing waves of Vietnamese settlers which followed overwhelmed the Khmer kingdom—weakened as it was due to war with Thailand—and slowly Vietnamized the area.