[5] On November 19, 2005, its workers finished replacing all four steam generators in 63 days, 13 hours, a world record for a four-loop plant.

On December 24, 2020, an electric fault on the non-safety main generator caused an extensive outage requiring the replacement of significant components.

[12] On July 28, 2008, Ameren Missouri applied to the U.S. Nuclear Regulatory Commission (NRC) for a Combined Construction and Operating License (COL) to build a 1,600-MW Areva Evolutionary Power Reactor.

One stumbling block was a law that forbids utilities to charge customers for the interest accrued on a construction loan before a new plant produces electricity.

[15][16] In April 2012, Ameren Missouri and Westinghouse Electric Company announced their intent to seek federal funding for a new generation of nuclear reactors to be installed at the Callaway site.

[20] Another 5,000 US gallons (19,000 L; 4,200 imp gal) of water are sent to the Missouri River as "blowdown" to flush solids from the cooling tower basin.

[22] In August 2010, the Nuclear Regulatory Commission's estimated that the annual chance that an earthquake might damage the core at Callaway was 1 in 500,000,[23][24] the lowest probability of any U.S. reactor.