The North Split will close on by Sunday and remain closed for about 18 months as crews rebuild and reconfigure part of the highway.
This is the second most highly traveled interchange in the state.
The southbound lanes will close between the North Split and Washington Street.
The Indiana Department of Transportation is asking drivers to be patient as their commute will increase and map out alternative routes to prepare.
“When we close it this weekend it is going to take some growing pains, especially for locals to get around,” INDOT Communications Director Mallory Duncan said. “So the first couple weeks are probably going to be a little painful as people try to get around and choose their route on a weekday versus weekend and what city streets will work best for me.”