At the start of his career, Pavelić was a lawyer and a politician of the Croatian Party of Rights in the Kingdom of Yugoslavia known for his nationalist beliefs and support for an independent Croatia. By the end of the 1920s, his political activity became more radical as he called on Croats to revolt against Yugoslavia, and schemed an Italian protectorate of Croatia separate from Yugoslavia. After King Alexander I declared his 6 January Dictatorship in 1929 and banned all political parties, Pavelić went abroad and plotted with the Internal Macedonian Revolutionary Organization (IMRO) to undermine the Yugoslav state, which prompted the Yugoslav authorities to try him in absentia and sentence him to death. In the meantime, Pavelić had moved to fascist Italy where he founded the Ustaše, a Croatian nationalist movement with the goal of creating an independent Croatia by any means, including the use of terror. Pavelić incorporated terrorist actions in the Ustaše program, such as train bombings and assassinations, staged a small uprising in Lika in 1932, culminating in the assassination of King Alexander in 1934 in conjunction with the IMRO. Pavelić was once again sentenced to death after being tried in France in absentia and, under international pressure, the Italians imprisoned him for 18 months, and largely obstructed the Ustaše in the following period.
At the behest of the Germans and Italians, senior Ustaša Slavko Kvaternik declared the NDH's establishment in the name of Pavelić, the Poglavnik. Pavelić returned and took control of the puppet government, creating a political system similar to that of Fascist Italy and Nazi Germany. The NDH, though constituting a Greater Croatia, was forced by the Italians to relinquish several territorial concessions to the latter. After taking control, Pavelić imposed largely anti-Serbian and antisemitic policies that resulted in the deaths of over 100,000 Serbs and Jews in concentration and extermination camps in the NDH, murdering and torturing several hundred thousand Serbs, along with tens of thousands of Jews and Roma. These persecutions and killings have been described as the "single most disastrous episode in Yugoslav history". The racial policies of the NDH greatly contributed to their rapid loss of control over the occupied territory, as they fed the ranks of both the Chetniks and Partisans and caused even the German authorities to attempt to restrain Pavelić and his genocidal campaign.
In 1945, he ordered the executions of prominent NDH politicians Mladen Lorković and Ante Vokić on charges of treason when they were arrested for plotting to oust him and align the NDH with the Allies. Following the surrender of Germany in May 1945, Pavelić ordered his troops to keep fighting even after the surrender. The remainder of the NDH government decided to flee to Austria on 3 May 1945, but Pavelić instead ordered them to retreat to Austria over the former border of the Third Reich and have the Croatian Armed Forces surrender to the British Army. The British refused to accept the surrender and directed them to surrender to the Partisans. The Partisans began carrying out massacres against the Ustaše when the latter attacked their position, killing them in a series of repatriations later known as the Bleiburg repatriations. Pavelić himself fled to Austria, and later Argentina, whose president Juan Perón provided sanctuary for German war criminals and several Ustaše. On 10 April 1957, he was shot several times in a failed assassination attempt by the Serbian assassin Blagoje Jovović. Pavelić survived the attempt and soon left Argentina for Spain. He died two and a half years later, on 28 December 1959, aged 70, from the injuries he sustained in the attempted assassination.