Initially he took piano lessons with a private tutor. At the age of 12, in 1872, he went to Warsaw and was admitted to the Warsaw Conservatorium. After graduating in 1878, he was asked to become a tutor of piano classes at his alma mater, which he accepted. In 1880 Paderewski married Antonina Korsakówna, and soon afterwards, their first child was born. The following year, they discovered that the son was handicapped; soon afterward, Antonina died. Paderewski decided to devote himself to music, and in 1881 he went to Berlin to study music composition with Friedrich Kiel and Heinrich Urban. In 1884 he moved to Vienna, where he was a pupil of Theodor Leschetizky. It was in Vienna that he made his musical debut in 1887. He soon gained great popularity and his subsequent appearances (in Paris in 1889, and in London in 1890) were major successes. His brilliant playing created a furore which reached to almost extravagant lengths of admiration; and his triumphs were repeated in the United States in 1891. His name at once became synonymous with the highest level of piano virtuosity. However, not everyone was impressed. After hearing Paderewski for the first time, Moriz Rosenthal said: "Yes, he plays well, I suppose, but he's no Paderewski".

In 1899 he married Baroness de Rosen.

He was also a substantial composer, including many pieces for piano. In 1901 his sole opera Manru received its world premiere at Dresden, then it had its American premiere in 1902 at the Metropolitan Opera. To this day it remains the only Polish opera by a Polish composer ever performed there.

Paderewski, his second wife, entourage, parrot and Erard piano travelled to Auckland, New Zealand, from Sydney, Australia, aboard the steamer Zealandia on 28 August 1904. He travelled to Wellington by train and gave a concert there on 12 September.

He was also active in pursuing various philanthropic causes. In 1910 he funded the erection of the Battle of Grunwald Monument in Kraków, in commemoration of the 500th anniversary of the event. In 1913, Paderewski settled in the United States.

On the eve of World War I, and at the height of his fame, Paderewski bought a 2,000-acre (8.1 km²) property, Rancho San Ignacio, near Paso Robles, in San Luis Obispo County, on the central coast of California. A decade later he planted Zinfandel vines on the California property. When the vines matured, the wine was made for him at the nearby York Mountain Winery, then, as now, one of the best-known wineries between Los Angeles and San Francisco.

He was extremely popular internationally, to such an extent that the music hall duo "The Two Bobs" had a hit song in 1916, in music halls across Britain, with the song "When Paderewski plays".

During World War I, Paderewski became an active member of the Polish National Committee in Paris, which was soon accepted by the Entente as the representative of Poland. He became a spokesman of that organisation, and soon also formed other social and political organisations, among them the Polish Relief Fund in London. It was then that he met the English composer Edward Elgar, who used a theme from Paderewski's Fantasie Polonaise in his work Polonia written for the Polish Relief Fund concert in London on 6 July 1916.

In April 1918, he met in New York City with leaders of the American Jewish Committee, including Louis Marshall, in an unsuccessful attempt to broker a deal whereby organized Jewish groups would support Polish territorial ambitions in exchange for support for equal rights. However, it soon became clear that no plan would satisfy both Jewish leaders and Roman Dmowski, head of the Polish National Committee.

At the end of the war, with the fate of the city of Poznań and the whole region of Greater Poland (Wielkopolska) still undecided, Paderewski visited Poznań. With his public speech on 27 December 1918, the Polish inhabitants of Poznań began a military uprising against Germany, called the Greater Poland Uprising.

In 1919, in the newly independent Poland, Paderewski became the Prime Minister and Minister of Foreign Affairs (January 1919 - December 1919), and he thus represented Poland at the Paris Peace Conference. In the summer of that year, he signed the Treaty of Versailles, which restored the territories of Greater Poland and Pomerania around the City of Gdańsk to Poland. Although this fell short of what the Polish delegates had demanded, these territories provided the core of the restored Polish state.

After being abandoned by many of his political supporters, Paderewski handed Piłsudski a letter of resignation on 4 December 1919, whereupon he took on the role of Polish Ambassador to the League of Nations.

In 1922 he retired from politics and returned to his musical life. His first concert after a long break, held at Carnegie Hall, was a significant success. He also filled Madison Square Garden (20,000 seats) and toured the United States in a private railway car.

Soon he moved to Morges in Switzerland. After Piłsudski's coup d'état in 1926, Paderewski became an active member of the opposition to Sanacja rule. In 1936 a coalition of members of the opposition was signed in his mansion; it was nicknamed the Front Morges after the name of the village.

By 1936, two years after the death of his wife, Paderewski consented to appear in a film presenting his talent and art on the screen. This proposal had come at a time when Paderewski did not wish to appear in public. However, the film project did proceed, and the selected film script was an opportunity to feature Paderewski. The film Moonlight Sonata was filmed throughout 1936.

In November 1937 Paderewski agreed to take on one last pupil for piano. This musician was Witold Małcużyński, who had won second place at the International Frédéric Chopin Piano Competition.

After the Polish Defensive War of 1939 Paderewski returned to public life. In 1940 he became the head of the Polish National Council, a Polish parliament in exile in London. The eighty year old artist also restarted his Polish Relief Fund and gave several concerts (most notably in the United States) to gather money for it. However, his mind was not what it had once been: scheduled again to play Madison Square Garden, he refused to appear, insisting that he had already played the concert, presumably remembering the concert he had played in the 1920s.

In addition to his concert tours, Paderewski was a popular speaker who was renowned for his wit, and was often quoted. He was once introduced to a polo player with the words: "You are both leaders in your spheres, though the spheres are very different." "Not so very different," Paderewski replied. "You are a dear soul who plays polo, and I am a poor Pole who plays solo." In another incident, Paderewski once recalled, "I established a certain standard of behaviour, that, during my playing, there must be no talking. When they began to talk, I would stop. I would say, 'I am sorry to interrupt your conversation. I deeply regret that I am obliged to disturb you, so I am going to stop for a while to allow you to continue talking.' You can imagine the effect it had..."

During one such tour in 1941, Paderewski was taken ill on 27 June. Nothing was discussed with his personal secretary or entourage. But at the initiative of Sylwin Strakacz, physicians were called in for consultation and diagnosed pneumonia. Despite increasing health and signs of recovery Paderewski died suddenly in New York, at 11:00 p.m. on 29 June. He was buried in Arlington National Cemetery, in Arlington Virginia, near Washington DC. In 1992, his body was brought to Warsaw and placed in St. John's Cathedral. His heart is encased in a bronze sculpture in the National Shrine of Our Lady of Czestochowa near Doylestown, Pennsylvania.

The Polish Museum of America in Chicago received a donation of the personal possessions of Ignacy Jan Paderewski following his death in June 1941. Both Ignacy Paderewski and his sister, Antonina Paderewska Wilkonska were enthusiastic supporters and generous sponsors of the Museum. Antonina, executor of Ignacy’s will, decided to donate these personal possessions to the Museum. In addition, the management of the Buckingham Hotel in New York City, where Ignacy spent the last months of his life, allowed Antonina to obtain the furnishings from the suite of rooms he had occupied. These furnishings were also donated to the Museum. With the assistance of Ignacy’s personal secretary, the furnishings and his personal mementos were arranged for public display in the room that had been the first display room of the Museum in 1937. This revised space was officially re-opened with a special dedication ceremony on 3 November 1941, three days before the date that would have marked Paderewski's 81st birthday.

In 1948 the Ignacy Paderewski Foundation was established in New York City, on the initiative of the Polish community in New York with the goal of promoting Polish culture in the United States. Two other Polish - American organizations are also named in his honor and dedicated to promoting the legacy of the maestro: The Paderewski Association in Chicago as well as the Paderewski Music Society in Southern California.

Due to the unusual combination of the notable achievements of being a world class pianist and a successful politician, Paderewski has become a favourite example for philosophers, and is often discussed in relation to Saul Kripke's "A Puzzle about Belief" for having a name that denotes two distinct qualities, that of being a politician and that of being a pianist.

Nowadays there are streets and schools named after Paderewski in many major cities in Poland. There are also streets named after him in Perth Amboy, New Jersey, and Buffalo, New York. In addition, the Academy of Music in Poznań is named after him. Paderewski even has his own star on the famous Hollywood Walk of Fame in Los Angeles.

In 1925 he was made an honorary Knight Grand Cross of the Order of the British Empire. This entitled him to the postnominal letters GBE but not to be known as "Sir Ignacy" (despite the erroneous claim in Time magazine), that title being reserved for British citizens. He was also awarded Doctorate honoris causa by the universities in Lwów (1912), Kraków (1919) and Poznań (1924), as well as several universities in the United States