Reinforced with some 3000 llaneros under command of Francisco Tomás Morales, he marched on the major port city of Cartagena de Indias.

In March 1815, Simón Bolívar was advancing to take Santa Marta and requested extra men and supplies from Cartagena, but the city's Governor general, Manuel del Castillo y Rada refused to support him.

The siege was lifted on 8 May and a disillusioned Bolivar, who had lost half his army to disease and desertion against a so-called ally, left New Granada for Jamaica.

Morillo was informed that the Republican authorities not only had not evacuated the residents of Cartagena, but also had allowed the surrounding population to take refuge in the fortress, thereby increasing the number of besieged to 18,000 people.

The Spaniards twice tried to capture Tesca Lagoon in order to strengthen the naval blockade of the fortress, but both times they were forced to retreat, having suffered heavy losses.

On 11–12 November, an assault was launched on two key defensive points - the Corma heights, where the Candelario monastery was located, turned by the Republicans into a real fortress, and the island of Tierrabomba.

At the most critical moment of the battle, the patriots were supported by the cannons of Castle San Felipe de Barajas, and the Spaniards were forced to abandon further attempts to break through to Cartagena from land.

In Cartagena, many Republicans who hadn't been able to escape over sea were executed, including Manuel del Castillo y Rada and José María García de Toledo as part of a group later known as the 9 Martyrs.