In 1798 Pierpont Edwards of Connecticut paid $2500.00 for the 25 square miles (65 km²) of wilderness in modern-day Trumbull County, Ohio that was later known as Mesopotamia Township.

The following spring, John Starke Edwards, just out of college, journeyed alone on foot, carrying an ax and knapsack, across the Pennsylvania frontier into the tangled forest. He cut the first tree that ever felled by an ax upon his father's land. The fragrance which the sunshine drew out of a rich forest floor set him agog with plans to get a settlement started. He offered a hundred acres (0.4 km²) of free land to the first five families to come and stay five years, and fifty acres (0.2 km²) to the first five single men. These men were Seth Tracey, Capt. Hezekiah Sperry, Joseph Noyles, Otis Guild, and Dr. Joseph Clark.

Beginning in 1809, mail was brought on foot from Warren and left in Seth Tracy's hat. Our town was then in the District of Troy, but mail mix-ups with the other two Troys in Ohio bothered residents. To resolve this, the name Mesopotamia, meaning "land between two rivers," was chosen in 1819. Like the Near Eastern land of that name, it is located between two fertile streams: the Grand and the Cuyahoga Rivers.

Today, Mesopotamia encompasses 36 square miles (93 km²) with the land being valued at $21,263,400. The population is 2600, with about 60% of the population being the Amish community