On October 21, 1805, he received his baptism of fire at the battle of Trafalgar, where he served aboard the San Juan Nepomuceno where he would be wounded and taken prisoner by the English.

[2] On April 11, 1811, he took part in the decision of the people of Getsemani, who, in sympathy with the city of Cartagena, joined in the proclamation of independence of Cundinamarca, thus disregarding the authority of the metropolis.

As second-in-command to Admiral Luis Brión he arrived at Riohacha on March 12, 1820, where he fought in the battles of Laguna Salada, Pueblo Viejo, Tenerife, La Barra, Ciénaga de Santa Marta and San Juan.

This time he was invested with the office of commander-general of the Third Department of the Navy and of the Zulia Theater of Operations; on this position, he did a brilliant job that culminated on July 24, 1823, in the naval battle of Lake Maracaibo, in which he defeated the Spanish squadron, which led to the capitulation of the field marshal Francisco Tomás Morales the following August 3, 1823.

Padilla seems to have refused and there is no record of his escape, but he was judged by a tribunal for the charge of conspiracy, then sentenced to death and executed in the Plaza de la Constitución in Bogotá on 2 October 1828.

The remains of Admiral Padilla lie inside the Cathedral of Our Lady of Remedios in Riohacha, which was declared in his honor as a Cultural Heritage of the Colombian nation.

In 2023, in commemoration of the 200th anniversary of the Naval Battle of Lake Maracaibo the Central Bank of Colombia released a commemortaive coin with a value of $10,000 COP, the obverse side of the coin includes the image of Admiral José Padilla López with the inscription of the phrase "Morir o ser libres” (To die or to be free) which was a proclamation to his men before the historic battle started.