Sucre was born to a wealthy and prominent family in Cumaná which was then part of the Spanish Viceroyalty of Nueva Granada and the Captaincy-General of Venezuela, son of Vicente de Sucre y García de Urbaneja and wife María Manuela de Alcalá y Sánchez Ramírez de Arellano. There is some dispute as to his ancestry. According to one noted Venezuelan genealogist, Sucre is a descendant of Charles de Succre, a member of a French-Flemish family appointed by the king of Spain to be governor of Cuba. According to the German "Lexikon des Judentums", however, Sucre is a descendant of a Bavarian Jewish family named "Zucker".
In 1821, Bolívar put him in charge of the campaign to liberate Quito, and Sucre won a decisive victory at the Battle of Pichincha on May 14, 1822. Shortly after the battle, Sucre and Bolívar entered the newly-liberated Quito and Sucre was named President of the Province of Quito, much to his chagrin.
After the victory at Ayacucho, Bolívar would write his Resumen Sucinto de la Vida del General Sucre, a short biography full of flattering comments about his lieutenant. In a letter telling Sucre of the biography he had written, Bolívar said:
Believe me, General, nobody loves your glory as much as I do. Never has a Chief paid more glorious tribute to a lieutenant. At the moment it is being printed, a telling of your life done by myself; being faithful to my conscience I give you all that you deserve. I say this so that you can see that I am fair: I disapprove much what I do not think is right, but at the same time I admire that which is sublime.
In late 1828, at the urging of Bolívar, the Congress of Gran Colombia named him President of Congress. They also intended to name him president of the republic as Bolívar's would-be successor, but it never came to pass because Sucre likely would have it turned down. Sucre was named member of a commission, led by José Antonio Páez, that traveled to Venezuela in 1829 to quell political separatism among local authorities. The difficulty of this task added to Sucre's continuing dissatisfaction with Gran Colombia's political environment. In that year he had an only daughter by his marriage Teresa de Sucre y Carcelén, who was born in Quito on June 30, 1829 but died there on November 15, 1831.
In early 1830, when Sucre learned that Bolívar had resigned and intended to leave the country, he decided to go to Quito in order to resume his private life, but was shot from ambush near Pasto, at the Sierra de Berruecos in southern Colombia, on June 4, 1830.
The details of the murder were unclear and theories about the reason for it abound. One of the older and better documented theories says that José María Obando was the assassination's mastermind, and one of the alleged assassins named in this theory was later executed for his apparent role. Later theories implicated different (or additional) individuals, such as Juan José Flores, Agustín Gamarra, and Francisco de Paula Santander.
Some have argued that Sucre was assassinated so as to leave no clear successor to Bolívar. Sucre represented, according to historian Tomas Polanco Alcantara, "the indispensable complement to Simón Bolívar". When news of Sucre's death came to Bolívar, he said, "Se ha derramado, Dios excelso, la sangre del inocente Abel..." ("The blood of the innocent Abel has been spilled, God almighty ..."). Bolivar later wrote (Gaceta de Colombia, July 4, 1830):
If he had breathed his spirit upon the theater of victory, with his last breath he would have given thanks to heaven for having given him a glorious death; but cowardly murdered in a dark mountain, he leaves his fatherland the duty of persecuting this crime and of adopting measures that will curb new scandals and the repetition of scenes as lamentable and painful as this.
The department of Sucre in Colombia and the city of Sucre in Bolivia are named for him. The former currency of Ecuador was the sucre, and the State of Venezuela in which he was born, Cumaná, was renamed Sucre. A large neighborhood in the city of Caracas is named Sucre. Some of his descendants in Venezuela have followed in his military and political footsteps.
Antonio José de Sucre is buried in the Cathedral of Quito, Ecuador, as it was expressed by him in life "I want my bones to be forever in Quito".