He was born on November 14, 1875 to Fernando H. del Pilar and Felipa Sempio of San Jose, Bulacan, Bulacan. His uncle was Marcelo H. del Pilar and another uncle, Toribio H. del Pilar was exiled to Guam after the Cavite Mutiny of 1872.

He enrolled at the Ateneo de Manila and lived with his uncle, Deodato Arellano. He finished his Bachelor of Arts in 1896 but the Revolution broke out thus he stopped studying. He and other young Bulakeños presented themselves for military service. For his daring attacks in various encounters, he was steadily promoted in the military. Aguinaldo took notice of the young man. Gregorio was one of the signers of the Pact of Biak-na-Bato and he later joined Aguinaldo in exile in Hongkong. He became Aguinaldo’s protégé and confidential man. On May 1898, upon resumption of hostilities against Spain, Aguinaldo designated him Dictator of the province of Bulacan and Nueva Ecija. On June 1, 1898, he landed at Kay Luntaw with rifles, established his headquarters at Matungao and started the seige of Bulacan. The Spanish troops signed the terms of surrender for the Spaniards while Gen. Gregorio del Pilar signed for the Filipino troops. He continued his battles in Manila, Caloocan and Bulacan. He was sent to represent the military and the President in the two peace missions offering a ceasefire to the Americans after the fall of Malolos. He was made the Military Governor of Pangasinan and the right hand man of Gen. Aguinaldo. On November 22 he was ordered to defend and protect the Tirad Pass to cover the retreat of President Aguinaldo. On the morning of December 2, 1899, Americans of the 33rd Infantry Volunteers under Major Payton C. March stormed Tirad Pass. With the aide of a spy, Jose Galut, He revealed a secret approach to the Americans. This caused the defeat of the troops of Gregorio del Pilar. An American officer, Lt. Dennis P. Quinlan ordered his men to give honor to the fallen but valorous foe. Likewise, the National Historical Institute and his town mates in Bulacan also gave him highest the recognitions.