From Nashville, Tennessee (Approx: 135 miles):

From Nashville, travel Southwest on I-40 to I-65.  Take I-65 South to U.S. Highway 72 (Athens, AL).  Travel West on U.S. Highway 72 for approximately 45 miles.  This will bring you into Florence.

From Chattanooga, Tennessee (Approx: 175 miles):

From Chattanooga, travel West on I-24 to U.S. Highway 72.   Take Highway 72 West for approximately 110 miles.  This will bring you into Florence.

From Atlanta, Georgia (Approx: 260 miles):

From Atlanta, travel West on I-20 to Birmingham.   In Birmingham, take I-20 to I-65.  Take I-65 North to Alabama Highway 157 (University of North Alabama Highway).  Take Highway 157 Northwest for approximately 60 miles.  This will bring you into U.S. Highway's 72 & 43 in Muscle Shoals/Tuscumbia.  Follow Hwy 43 (Woodward Avenue) into Florence.

Alternate Route from Atlanta:

From Atlanta, travel West on I-20 to Birmingham.   In Birmingham, take I-20 to I-65.  Take I-65 North to U.S. Highway 72 (Athens, AL).  Travel West on U.S. Highway 72 for approximately 45 miles.  This will bring you into Florence.

From Birmingham, Alabama (Approx: 120 miles):

Take I-65 North to Alabama Highway 157 (University of North Alabama Highway).  Take Highway 157 Northwest for approximately 60 miles.   This will bring you into U.S. Highway's 72 & 43 in Muscle Shoals/Tuscumbia.  Follow Hwy 43 (Woodward Avenue) into Florence.

Alternate Route from Birmingham:

Take I-65 North to U.S. Highway 72 (Athens, AL).   Travel West on U.S. Highway 72 for approximately 45 miles.  This will bring you into Florence.

From Huntsville, AL (Approximately 65 miles):