In 1860 he, alongside Giuseppe Garibaldi, led the "expedition of the thousand" which disembarked on Sicily on 11 May 1860. On the 13th, Crispi drew up the Proclamation of the Kingdom of Italy. After the fall of Palermo, Crispi was appointed minister of the interior and of finance in the Sicilian provisional government, but was shortly afterwards obliged to resign on account of the struggle between Garibaldi and the emissaries of Count Camillo Benso di Cavour on the question of timing of the annexation of Sicily by Italy.
Appointed secretary to Garibaldi, Crispi secured the resignation of Agostino Depretis, whom Garibaldi had appointed pro-dictator, and would have continued his fierce opposition to Cavour at Naples, where he had been placed by Garibaldi in the foreign office, had not the advent of the Italian regular troops and the annexation of the Two Sicilies to Italy brought about Garibaldi’s withdrawal to Caprera and Crispi’s own resignation.
Entering parliament in 1861 as deputy of the extreme Left for the Castelvetrano commune, Crispi acquired the reputation of being the most aggressive and most impetuous member of the republican party. In 1864, however, he announced he was a monarchist, in the famous phrase afterwards repeated in his letter to Mazzini:
In 1866 he refused to enter Baron Bettino Ricasoli’s cabinet; in 1867 he worked to impede the Garibaldian invasion of the papal states, foreseeing the French occupation of Rome and the disaster of Mentana. By methods of the same character as those subsequently employed against himself by Felice Cavallotti, he carried on the violent agitation known as the Lobbia affair, in which sundry conservative deputies were, on insufficient grounds, accused of corruption. On the outbreak of the Franco-German War he worked energetically to impede the projected alliance with France, and to drive the Giovanni Lanza cabinet to Rome. The death of Urbano Rattazzi in 1873 induced Crispi’s friends to put forward his candidature to the leadership of the Left; but Crispi, anxious to reassure the crown, secured the election of Depretis.
In 1876 he was elected President of the Chamber. During the autumn of 1877 he went to London, Paris and Berlin on a confidential mission, establishing cordial personal relationships with British Prime Minister William Gladstone and Foreign Minister Lord Granville and other English statesmen, and with Otto von Bismarck, by then Chancellor of the German Empire.
In December 1877 he replaced Giovanni Nicotera as minister of the interior in Depretis’s cabinet. Although his short term of office lasted just 70 days, they were instrumental in establishing a unitary monarchy. On January 9, 1878, the death of Victor Emmanuel and the accession of King Umberto enabled Crispi to secure the formal establishment of a unitary monarchy, the new monarch taking the title of Umberto I of Italy instead of Umberto IV of Savoy. On the 9 February, 1879, the death of Pope Pius IX necessitated a conclave, the first to be held after the unification of Italy. Crispi, helped by Mancini and Cardinal Pecci (afterwards Leo XIII), persuaded the Sacred College to hold the conclave in Rome, establishing the legitimacy of the capital.
For nine years Crispi remained politically under a cloud, but in 1887 returned to office as minister of the interior in the Depretis cabinet. Following Depretis’s death on July 29, 1887 Crispi assumed the premiership of his country.
In 1894 he was threatened with expulsion from the Masonic Grande Oriente d'Italia for being too friendly towards the Catholic Church. He had previously been strongly anticlerical but had become convinced of the need for rapproachment with the Papacy.
Crispi’s uncompromising suppression of disorder, and his refusal to abandon either the Triple Alliance or the Eritrean colony, or to forsake his colleague Giorgio Sidney Sonnino, caused a breach between him and the radical leader Felice Cavallotti. Cavallotti then began against him a pitiless campaign of defamation. An unsuccessful attempt upon Crispi’s life by the anarchist Lega brought a momentary truce, but Cavallotti’s attacks were soon renewed more fiercely than ever. They produced so little effect that the general election of 1895 gave Crispi a huge majority, but, a year later, the humiliating defeat of the Italian army at Adwa in Ethiopia brought about his resignation. The ensuing Antonio di Rudini cabinet lent itself to Cavallotti’s campaign, and at the end of 1897 the judicial authorities applied to the chamber for permission to prosecute Crispi for embezzlement. A parliamentary commission, appointed to inquire into the charges against him, discovered only that Crispi, on assuming office in 1893, had found the secret service coffers empty, and had borrowed money from a state bank to fund it, repaying it with the monthly instalments granted in regular course by the treasury. The commission, considering this proceeding irregular, proposed, and the chamber adopted, a vote of censure, but refused to authorize a prosecution. Crispi resigned his seat in parliament, but was re-elected by an overwhelming majority in April 1898 by his Palermo constituents. For some time he took little part in active politics, chiefly on account of his growing blindness. A successful operation for cataract restored his eyesight in June 1900, and notwithstanding his 81 years he resumed to some extent his former political activity. Soon afterwards, however, his health began to give way permanently, and he died at Naples on 12 August 1901.