A conclave was held from 25 to 28 October 1958 to elect a pope to succeed Pius XII, who had died on 9 October 1958. Of the 53 eligible cardinal electors, all but two attended. On the eleventh ballot, the conclave elected Cardinal Angelo Roncalli, the patriarch of Venice. After accepting his election, he took the name John XXIII. He was the second patriarch of Venice to be elected pope in the 20th century, after Pius X in the 1903 conclave. John XXIII's coronation took place on 4 November 1958.

The communist governments of Hungary and Yugoslavia prevented Cardinals József Mindszenty and Aloysius Stepinac from traveling to Rome. In comparison with the 1922 conclave, when three cardinals failed to reach Rome in time when the conclave opened 10 days after the pope's death as required; or the 1939 conclave, when three cardinals reached Rome on the morning the conclave opened 18 days after the pope's death under new rules; all the cardinals who made the trip reached Rome by 22 October, with few days to spare before the conclave began 16 days after Pius XII's death.

For the first time, the speed of travel matched the internationalization of the College of Cardinals, thanks to advancements in air travel. As one newspaper put it, "The archbishop of New York can reach Rome today faster than the archbishop of Palermo did a generation ago." This conclave included cardinals from 21 countries compared to 16 at the previous conclave, and 18 non-Europeans compared to seven. The 17 Italians out of 51 represented their lowest percentage since 1455.

The cardinals anticipated a long conclave. There was no "dominating personality" as Pius XII had been in 1939, and the proverbial search for contrast ('fat pope, thin pope') suggested a "pastoral pope" to follow a "diplomatic pope". Another analysis set the likely age range between 55 and 70, with a preference for an Italian outside the Curia. Several papabili were discussed. The conservative Giuseppe Siri of Genoa, supportive of the Vatican's centralization of authority, was only 52, and his election would have meant another long papacy like that of Pius IX. The liberal Giacomo Lercaro of Bologna, more disposed to granting independence to local authorities, was 67. Angelo Roncalli had become the patriarch of Venice after more than 25 years in the diplomatic service of the Holy See in Bulgaria, Turkey and France. Approaching 77, his age marked him as a possible compromise choice in expectation of a short pontificate, along with his "reputation for being broad-minded and conciliatory". He also represented a combination of diplomatic and pastoral experience.

Gregorio Pietro Agagianian, the Catholic Armenian patriarch of Cilicia, had spent much of his adult life in Rome. He was relatively young at 63 and highly respected, but his non-Italian heritage would have made him a surprising choice. Other candidates mentioned were Ernesto Ruffini of Palermo and two Curia officials, Valerio Valeri and Alfredo Ottaviani. Benedetto Aloisi Masella, the 79-year-old veteran diplomat who was chosen as camerlengo on 9 October, was also mentioned as a compromise candidate with "his chances diminished because of his age". Also mentioned, in a radical departure from tradition, was Giovanni Montini, the archbishop of Milan, whom Pius XII had not made a cardinal. The New York Times cast a wide net, offering more than a dozen names, including two non-Italians, Paul-Émile Léger of Montreal and Manuel Goncalves Cerejeira of Lisbon. Life magazine's coverage included portraits of Agagianian, Lercaro, Montini, Ottaviani, Roncalli, Ruffini, Siri, and Valeri. As the press speculated about interest in a transitional pope and possible discussions among the cardinal electors, the Vatican's mouthpiece, L'Osservatore Romano denounced the "irresponsible lightness" with which the press approached the subject, especially its reports of electioneering. A Moscow radio broadcast criticized Pius XII for meddling in politics and hoped for a new pope that was devoted instead to the "religious problems".

Betting establishments reported Roncalli was favored by their clients, given 2 to 1 odds. By the second day of the conclave, after four ballots produced no results, speculation centered on Roncalli, Valeri, Masella, and Agagianian, the first three elderly and the last an unlikely outsider.

Pope Pius XII tried in the consistory of 1953 to bring the membership of the College of Cardinals to the maximum of 70, the limit established by Pope Sixtus V in the 16th century. On that occasion he named 24 cardinals. When one cardinal-designate, Carlo Agostini, died on 28 December at the age of 64, the Vatican announced another cardinal designate the next day, Valerian Gracias of India, so the College reached its full complement of 70 members, with 26 of them Italian.

Deaths in the intervening five years, including those of Celso Costantini on 17 October and Edward Mooney of Detroit on 25 October just hours before the start of the conclave, had reduced the College to 53 members. József Mindszenty feared the Communist government of Hungary would not allow him to return if he attended the conclave, and government authorities refused to grant him safe conduct despite a request by the U.S. State Department at the request of the College of Cardinals. Aloysius Stepinac was too ill to travel from Zagreb, and he was forbidden from leaving Yugoslavia as a condition of his release from prison in 1951.