Officials say, if the river rises to an unsafe level, bridges will be impassable for both northbound and southbound lanes of I-75 and the interstate would be closed immediately.
Additional bridges may be impacted, including U.S. Highway 27, U.S. Highway 47, State Road 47 and possibly U.S. Highway 121.
The problems in Alachua County came as Jacksonville have seen major flooding since Monday in areas around the St. Johns River.
The Florida Department of Transportation contacted 11Alive News early Wednesday warning that a small bridge near Mile Marker 408 in Florida may have to be closed due to rising waters.
The river level is now safe at 55 feet but if it rises to an unsafe level it would be shut down in both directions, officials said.
As of Wednesday morning, the river level is safe at 55 feet.
In the event of road flooding on I-75 at the Sante Fe River, FDOT will reroute traffic to USA 19, US 301 and I-95.
Occasional gridlock hit westbound I-4 out of Orlando and southbound I-75 into the Tampa Bay area near Spring Lake and farther south near Temple Terrace and Brandon.
Should the interstate close, drivers would have to detour to I-295 / I-95 or US-19 / US-98 / US-27. The stretch from Macon south to the Florida line appeared to have no delays.