Kennedy Onassis did not support that most of the White House showed little historical significance through its artifacts and furniture. She made it her first major project as first lady to restore its historical significance. She decided to make the family living area more suitable for family life by adding a kitchen on the family floor and new rooms for her children. She created a fine arts committee to find the funding for her restoration process of the White House. She also wanted to redesign and replant most of the Rose Garden and the East Garden, which was renamed the Jacqueline Kennedy Garden after her husband's assassination. Kennedy Onassis helped stop the destruction of historic homes in Lafayette Square in Washington, D.C., because she felt these buildings were an important part of the nation's capital and its history.
Before she became first lady, presidents and their families had taken furniture and other items from the White House when they left office; this led to the lack of original historical pieces. She personally wrote to possible donors in order to track down these missing furniture and other historical pieces of interest. Kennedy Onassis supported a Congressional bill saying that the White House furnishings would be the property of the Smithsonian Institution rather than available to an ex-president to claim as their own. She also founded the White House Historical Association, the Committee for the Preservation of the White House, the position of a permanent Curator of the White House, the White House Endowment Trust, and the White House Acquisition Trust.
On February 14, 1962, Kennedy Onassis took American television viewers on a tour of the White House on CBS News. In the tour, she stated that "I feel so strongly that the White House should have as fine a collection of American pictures as possible. It's so important ... the setting in which the presidency is presented to the world, to foreign visitors. The American people should be proud of it. We have such a great civilization. So many foreigners don't realize it. I think this house should be the place we see them best". The event was watched by 56 million television viewers in the United States. Kennedy won a special Emmy Award in 1962, making her the only first lady to win an Emmy.
Throughout her husband's presidency and more than any of the first ladies before her, Kennedy Onassis made many official visits to other countries, on her own or with the President to a popular response. In 1961, the Kennedys began their official trip of Europe in France. After arriving in the country, many liked her including President of France Charles de Gaulle because of her ability to speak French and her knowledge of French history. ​"Time" magazine gave a positive note about the trip saying "There was also that fellow who came with her". Even President Kennedy joked, "I am the man who accompanied Jacqueline Kennedy to Paris – and I have enjoyed it!"
From France, the Kennedys traveled to Vienna, Austria, where Soviet Premier Nikita Khrushchev was asked to shake the President's hand for a photo. He replied, "I'd like to shake her hand first". The U.S. Ambassador to India John Kenneth Galbraith recommended Kennedy Onassis to begin a tour in India and Pakistan with her sister Lee Radziwill in 1962. President of Pakistan Ayub Khan, had given her a horse named Sardar as a gift. He had found out on his visit to the White House that he and the First Lady had a common interest in horses. "Life" magazine wrote that Kennedy "conducted herself magnificently", however found that her crowds were smaller than those that President Dwight Eisenhower and Queen Elizabeth II.
Kennedy Onassis would later travel to other countries including Afghanistan, Austria, Canada, Colombia, United Kingdom, Greece, Italy, Mexico, Morocco, Turkey, and Venezuela representing the United States and her husband's administration. Unlike her husband, Kennedy Onassis was fluent in Spanish, which she used to address Latin American audiences.
In early 1963, Kennedy was again pregnant, with the couple's third child. She spent most of the summer at a home she and the President had rented near the Kennedy Compound on Cape Cod, Massachusetts.
On August 7, five week early of her due date, she went into labor and gave birth to a boy, Patrick Bouvier Kennedy through an emergency Caesarean section at nearby Otis Air Force Base. The infant's lungs were not fully developed, and he was transferred from Cape Cod to Boston, where he died of hyaline membrane disease two days after birth. Kennedy was at Otis Air Force Base to recovery after the Caesarean delivery; her husband went to Boston to be with their infant son and was there when he died. On August 14, the President returned to Otis to take her home and gave a speech to thank nurses and airmen who had cared for her. As a thank you, Kennedy Onassis gave the hospital staff a framed and signed lithographs of the White House.
Kennedy Onassis's health was affected by Patrick's death because she suffered from depression shortly afterwards. However, the loss of their child helped the Kennedy's marriage and brought the couple closer together as they both mourned the loss of Patrick. Before Patrick's death, Kennedy Onassis was distant with her husband after rumors of him having affairs with secretaries and socialites. It was rumored that Kennedy had extramarital affairs with Marilyn Monroe, Marlene Dietrich, Pamela Turnure, Angie Dickinson and Blaze Starr.
On November 21, 1963, the Kennedys went on a political trip to Texas to get more support for her husband's 1964 campaign. After a breakfast on November 22, they took a very short flight on Air Force One from Fort Worth's Carswell Air Force Base to Dallas's Love Field with Texas Governor John Connally and his wife Nellie. Kennedy Onassis was wearing a bright pink Chanel suit and a pillbox hat, President Kennedy personally picked for her to wear. A motorcade was to take them to the Trade Mart, where the president was set to speak at a lunch. Kennedy Onassis was sitting next her husband's left in the third row of seats in the presidential limousine.
After the motorcade turned the corner onto Elm Street in Dealey Plaza, Kennedy Onassis heard loud bangs and she thought it was a motorcycle backfiring and did not realize that it was a gunshot until she heard Governor Connally scream. Within 8.4 seconds, two more shots had rung out, and one of the shots struck her husband in the head. She quickly began to climb onto the back of the limousine. Secret Service agent Clint Hill later told the Warren Commission that he thought she had been reaching across the trunk for a piece of her husband's skull that had been blown off. Hill ran to the car and jumped onto it, telling her back to go back to her seat. She would later say that she saw pictures "of me climbing out the back. But I don't remember that at all".
President Kennedy died not long afterward, aged 46. After her husband was pronounced dead, Kennedy did not want to remove her blood-stained clothing, telling Lady Bird Johnson that she wanted "them to see what they have done to Jack". She continued to wear the blood-stained pink suit as she boarded Air Force One and stood next to Lyndon B. Johnson when he took the oath of office as the 36th President of the United States. The suit was donated to the National Archives and Records Administration in 1964 and, because of an agreement with her daughter, Caroline, will not be placed on public display until 2103.