The university is sponsored by and affiliated with the Seventh-day Adventist Church, and is situated within 284 acres (1.15 km2) of mountainous land with a view of the Atlantic Ocean.

[7] In 1939, the Inter-American Division of Seventh-day Adventists decided to move the campus to Santa Clara from Bartle, Oriente Province and to upgrade the institution to that of a junior college.

At the time, the Antillian Union of Seventh-day Adventists included the Bahamas, Cuba, Puerto Rico, Haiti, and Jamaica.

[8] The Cuban Revolution's decisive Battle of Santa Clara in December 1958, took place within a few miles of Antillian College.

Brown, then president of the college, provided an eyewitness account for the Adventist flagship journal, the Review and Herald.

Bombing had destroyed transportation routes causing two hundred of the college's students to remain on campus during the Christmas season.

Around midnight, Saturday night, two barbudos from Ernesto (Che) Guevara column were posted to guard the college's building.

Brown further recounted, "We walked to the university campus and there found the commander, Dr. Ernesto (Che) Guevara (who had previously been befriended by Adventist),[10] with an assistant looking over the map of the city.

When we indicated that we had a problem in obtaining milk and food, he indicated that we were now in the Free Territory of Cuba, and that the rebel soldiers would see to it that we received all that was necessary.... At noon of that first day, about one hundred men came in for dinner.

Then she explained the procedure in our cafeteria, adding that it is our custom always to ask God to bless the food before we begin to eat.

Still other students and faculty members, together with some rebels, crowded into the hallways under the reinforced concrete floor of the new library.

When the plane persisted in its aim, he swam up the creek, with only his head above water, and remained so until the shooting was over.

[9] On New Year's Day, 1959, it seemed that the college would be able to continue on with its program in Cuba as the new Cuban leadership allowed it to operate with no restrictions.