Supported by Brazil and the Uruguayan liberals, he created the Grand Army and forced Manuel Oribe to capitulate, ending the long siege of Montevideo in October 1851, and finally defeating Rosas on 3 February 1852 at the Battle of Caseros.

In 1853, a constituent assembly adopted a constitution based primarily on the ideas of Juan Bautista Alberdi, and Urquiza was inaugurated president in March 1854.

[4] During his administration, foreign relations were improved, public education was encouraged, colonization was promoted, and plans for railroad construction was initiated.

Urquiza defeated the provincial army led by Bartolomé Mitre in October 1859, at the Battle of Cepeda, and Buenos Aires agreed to re-enter the Confederation.

He retired to San José Palace, his residence in Entre Ríos, where he ruled until he was assassinated at age 69 (along with his sons Justo and Waldino) by followers of dissident and political rival Ricardo López Jordán.