During the war, when a spinal ailment confined him to his bed for an entire year, Zobel discerned his artistic vocation. “I had all the time in the world to think and it was then that I started to consider the idea of becoming an artist.” He also devoted his time reading. At the end of the war, when he decided to enter the university in Manila, he realized that he had already read many of the titles assigned by his professors.

Upon entering Harvard in 1946, although he decided to read history and literature, the first thing he did was to buy a box of oil paints. Without any academic training, he decided to paint. Painting was partly the reason why he later stayed on as a bibliographical researcher at the university. Around this time, he met the Boston artists Reed Champion and Jim Pfeufer who helped him launch his career as an artist.