During World War II, he did a lot of portraits of American G.I.s and it was while sketching that he was discovered by Tony Velasquez. This eventually led to Velasquez inviting Santos to work on HALAKHAK KOMIKS in 1946, the Philippines' first serialized comic book. Santos contributed artwork for KIDLAT, written by Damy Velasquez.  Santos and Damy Velasquez's partnership will continue for two decades on DI-13 for Pilipino Komiks well into the late 60's before Santos moved to the US with his family.

"At the time I was doing DI-13, I was numerous dramatic novels, adventure strips, comedies, horror stories and whatever else the various publications that I was working for would assign to me."

Jesse Santos is one artist who has broken the suffocating norms of drawing that desire to capture the likeness of a subject by doing a style that is distinct and unique: presenting the essence of his subject. His work represents his subjects in a  personal and individual manner and it  has gained for him the respect of his peers and clients.

Known in the U.S. for his portraits of top American political figures and motion picture celebrities, Santos was among the first generation of Philippine Komiks artists. In the US, he contributed illustrations for books and magazines and for comic books including Dr. Spektor, Brothers of the Spear, Tragg, and Dagar.

The highly versatile Santos also designed the long-playing record album cover for folk singer Bobbie Gentry.

Santos has created murals, landscapes, movie ads and calendars. One such calendar shows a painting of the late Martin Luther King. In California, he was commissioned to do the portrait of Sen. George Zenovich and ex-President Jimmy Carter for the Modesto county office of Governor Brown.

He currently resides in California.