As a reward for his military service, Nathanael Greene was granted Mulberry Grove Plantation near Savannah, Georgia. The Greenes moved there with their children, hoping to establish a prosperous life as planters. The plantation presented both opportunities and challenges, including managing enslaved labor and dealing with financial difficulties.

Nathanael Greene died unexpectedly at the age of 44 from sunstroke while working in the fields. Caty was left a widow with several young children and significant debts. His death left the entire family with the daunting task of managing the plantation and settling his complex financial affairs.

Eli Whitney, a young inventor, arrived at Mulberry Grove Plantation, seeking work. Caty Greene offered him accommodation and encouraged him to develop a machine to process cotton more efficiently. Whitney invented the cotton gin, a revolutionary device that significantly increased cotton production.

Whitney's patent on the cotton gin was widely infringed, leading to years of legal battles. Caty Greene's role in encouraging and supporting Whitney is often debated. Some historians believe she may have contributed to the initial idea, although Whitney is officially credited with the invention. The cotton gin's impact on slavery was immense, as it increased the demand for enslaved labor, perpetuating and expanding the institution.

Caty Littlefield Greene died in Georgia at the age of 59. She experienced many hardships and successes, including the Revolution War and the birth of an innovation. She was later buried near Dungeness Mansion on Cumberland Island.