Some of the students who were shot had been protesting against the American invasion of Cambodia, which President Richard Nixon announced in a television address on April 30. Other students who were shot had been walking nearby or observing the protest from a distance.

There was a significant national response to the shootings: hundreds of universities, colleges, and high schools closed throughout the United States due to a student strike of four million students, and the event further affected the public opinion – at an already socially contentious time – over the role of the United States in the Vietnam War.

Richard Nixon had been elected President in 1968, promising to end the Vietnam War. In November 1969, the My Lai Massacre was exposed, prompting widespread outrage around the world and leading to increased public opposition to the war. In addition, the following month saw the first draft lottery instituted since World War II. The war had appeared to be winding down throughout 1969, so the new invasion of Cambodia angered those who believed it only exacerbated the conflict. Many young people, including college students and teachers, were concerned about being drafted to fight in a war that they strongly opposed. The expansion of that war into another country appeared to them to have increased that risk, although the number of troops serving in Vietnam had peaked in 1967, well before that time. Across the country, campuses erupted in protests in what Time called "a nation-wide student strike", setting the stage for the events of early May 1970.

President Richard Nixon announced to the nation that the "Cambodian Incursion" had been launched by United States combat forces.

At Kent State University, a demonstration with about 500 students was held on May 1 on the Commons (a grassy knoll in the center of campus traditionally used as a gathering place for rallies or protests). As the crowd dispersed to attend classes by 1 p.m., another rally was planned for May 4 to continue the protest of Nixon's expansion of the Vietnam war into Cambodia. There was widespread anger, and many protesters issued a call to "bring the war home." As a symbolic protest to Nixon's decision to send troops, a group of students watched a graduate student burning a copy of the U.S. Constitution while another student burned his draft card.

Trouble exploded in town around midnight when people left a bar and began throwing beer bottles at cars and breaking downtown store fronts. In the process they broke a bank window, setting off an alarm. The news spread quickly and it resulted in several bars closing early to avoid trouble. Before long, more people had joined the vandalism and looting.

By the time police arrived, a crowd of 120 had already gathered. Some people from the crowd had already lit a small bonfire in the street. The crowd appeared to be a mix of bikers, students, and transient people. A few members of the crowd began to throw beer bottles at the police, and then started yelling obscenities at them. The entire Kent police force was called to duty as well as officers from the county and surrounding communities. Kent Mayor Leroy Satrom declared a state of emergency, called Ohio Governor James Rhodes' office to seek assistance, and ordered all of the bars closed. The decision to close the bars early increased the size of the angry crowd. Police eventually succeeded in using tear gas to disperse the crowd from downtown, forcing them to move several blocks back to the campus.

City officials and downtown businesses received threats while rumors proliferated that radical revolutionaries were in Kent to destroy the city and university. Mayor Satrom met with Kent city officials and a representative of the Ohio Army National Guard. Following the meeting Satrom made the decision to call Governor Rhodes and request that the National Guard be sent to Kent, a request that was granted. Because of the rumors and threats, Satrom believed that local officials would not be able to handle future disturbances.

The decision to call in the National Guard was made at 5:00 P.M., but the guard did not arrive into town that evening until around 10 P.M.. A large demonstration was already under way on the campus, and the campus Reserve Officer Training Corps (ROTC) building was burning. The arsonists were never apprehended and no one was injured in the fire. More than a thousand protesters surrounded the building and cheered its burning. Several Kent firemen and police officers were struck by rocks and other objects while attempting to extinguish the blaze. Several fire engine companies had to be called in because protesters carried the fire hose into the Commons and slashed it. The National Guard made numerous arrests and used tear gas; at least one student was slightly wounded with a bayonet.

During a press conference, Governor Rhodes called the protesters un-American and referred to the protesters as revolutionaries set on destroying higher education in Ohio. "They're worse than the brown shirts and the communist element and also the night riders and the vigilantes," Rhodes said. "They're the worst type of people that we harbor in America. I think that we're up against the strongest, well-trained, militant, revolutionary group that has ever assembled in America." Rhodes can be heard in the recording of his speech yelling and pounding his fists on the desk.