He was born into an aristocratic family in Guayaquil, Ecuador, and as a youth, was sent to Madrid to finish his education. He returned to Ecuador in 1807, and committed himself to freeing his land, first from Spanish rule, and later from the Republic of Gran Colombia.
After Ecuadorian independence, Rocafuerte was elected a member of the National Congress for Pichincha Province. He led the opposition to President Juan José Flores, who exiled him to Peru.
Rocafuerte returned, and on September 20, 1833, became Governor of Guayas Province. He revolted against Flores, but was defeated and imprisoned. Because of the respect he was held in by his many supporters, Rocafuerte negotiated a settlement with Flores, and was released from prison. The settlement allowed Flores to finish his term in office, and promised Rocafuerte would become president afterwards, with Flores to head the army.
During his presidency, Rocafuerte passed a new constitution in 1835, and gave greater protection to Native Americans in Ecuador.
In 1839, after Rocafuerte had left office, Flores was again elected president, and for some time there were no difficulties between the two men. However, after electoral irregularities in 1843, Flores annulled the 1835 constitution and passed a new one, called by Rocafuerte 'The Letter of Slavery'. When Flores took up a third term as president in 1843, Rocafuerte left Ecuador in protest. After a short rebellion, Rocafuerte and Vicente Ramón Roca overthrew Flores on March 6, 1845, and Roca became president of Ecuador later that year.
Under Vicente Ramón Roca's presidency, Rocafuerte was appointed as special representative to various South American countries. He died on May 16, 1847.