Louisiana state officials said late on Friday that the Army Corps of Engineers would open the Morganza Spillway within the next 24 hours.
Louisiana Governor Bobby Jindal said the release of water would be slow.
The trigger for the spillway opening was when 1.5m cubic feet (42,500 cubic metres) of water per second was flowing down the Mississippi River at Red River Landing, just north of the Morganza Spillway.
That flow rate had already been reached, the National Weather Service said, according to Associated Press news agency.
Opening the spillway will channel water out of the flooded Mississippi River and into the Atchafalaya River basin, a low-lying area of central Louisiana, to avoid flooding Baton Rouge, New Orleans and other cities.
The Corps warned that if the spillway was not opened, New Orleans could be flooded by about 20 feet (six metres) of water.
Instead, water will flow south into the Atchafalaya Basin, flooding homes and farms in the state's Cajun country under an expected 10-20 feet of water.
Record flooding
The Morganza Spillway, 45 miles (72km) north-west of Baton Rouge, was last opened in 1973.
The flooding is approaching records set 84 years ago when hundreds of people in the region died.
At the Arkansas town of Helena, the river has crested at 56.5 feet.
The flood surge is expected to reach Vicksburg, Mississippi, on 19 May, reaching 57.5 feet - above the record 56.2 feet of 1927. The river begins overflowing its banks at Vicksburg at 43 feet.
It seems there is a remote possibility that the Mississippi might actually change its course and move some way to the west. That would be rather inconvenient for a lot of people:
'Never in my 30 years as a meteorologist have I witnessed a year like 2010--the astonishing number of weather disasters and unprecedented wild swings in Earth's atmospheric circulation were like nothing I've seen. The pace of incredible extreme weather events in the U.S. over the past few months have kept me so busy that I've been unable to write-up a retrospective look at the weather events of 2010. But I've finally managed to finish, so fasten your seat belts for a tour through the top twenty most remarkable weather events of 2010. At the end, I'll reflect on what the wild weather events of 2010 and 2011 imply for our future'.
