Prior to around year 400, the creek flowed from its headwaters west-northwesterly until the location of the present-day I-240/TN 385 interchange.

Around AD 400, a massive seismic event in the Ellendale Fault (part of the New Madrid Fault system) raised a low ridge across present-day east Memphis, diverting Nonconnah Creek away from the Wolf, causing it to flow directly into the Mississippi River several miles south of the Wolf's mouth.

The lowermost section of the Nonconnah that continued to flow into the Wolf eventually became known as Cypress Creek.

Nonconnah Creek was widened and channelized in the 20th century (like many of the rivers in West Tennessee) from its mouth to near Houston Levee Road in Collierville.

Under present day conditions, the 1934 and 1958 flood levels would cause considerably higher damages due to increased urbanization.

In the 1940s, the U.S. Army Corps of Engineers built an earthen levee system with pumping stations along the northern side of Nonconnah Creek from its mouth to Prospect Street in South Memphis.