Nuclear safety in the United States is governed by federal regulations issued by the Nuclear Regulatory Commission (NRC). The NRC regulates all nuclear plants and materials in the United States except for nuclear plants and materials controlled by the U.S. government, as well those powering naval vessels.

The 1979 Three Mile Island accident was a pivotal event that led to questions about U.S. nuclear safety. Earlier events had a similar effect, including a 1975 fire at Browns Ferry and the 1976 testimonials of three concerned GE nuclear engineers, the GE Three. In 1981, workers inadvertently reversed pipe restraints at the Diablo Canyon Power Plant reactors, compromising seismic protection systems, which further undermined confidence in nuclear safety. All of these well-publicised events, undermined public support for the U.S. nuclear industry in the 1970s and the 1980s. In 2002, the USA had what former NRC Commissioner Victor Gilinsky termed "its closest brush with disaster" since Three Mile Island's 1979 meltdown; a workman at the Davis-Besse reactor found a large rust hole in the top of the reactor pressure vessel.

Recent concerns have been expressed about safety issues affecting a large part of the nuclear fleet of reactors. In 2012, the Union of Concerned Scientists, which tracks ongoing safety issues at operating nuclear plants, found that "leakage of radioactive materials is a pervasive problem at almost 90 percent of all reactors, as are issues that pose a risk of nuclear accidents".

Following the Japanese Fukushima Daiichi nuclear disaster, according to Black & Veatch’s annual utility survey that took place after the disaster, of the 700 executives from the US electric utility industry that were surveyed, nuclear safety was the top concern. There are likely to be increased requirements for on-site spent fuel management and elevated design basis threats at nuclear power plants. License extensions for existing reactors will face additional scrutiny, with outcomes depending on the degree to which plants can meet new requirements, and some of the extensions already granted for more than 60 of the 104 operating U.S. reactors could be revisited. On-site storage, consolidated long-term storage, and geological disposal of spent fuel is "likely to be reevaluated in a new light because of the Fukushima storage pool experience".

In October 2011, the Nuclear Regulatory Commission (NRC) instructed agency staff to move forward with seven of the 12 safety recommendations put forward by the federal task force in July. The recommendations include "new standards aimed at strengthening operators’ ability to deal with a complete loss of power, ensuring plants can withstand floods and earthquakes and improving emergency response capabilities". The new safety standards will take up to five years to fully implement.