Holland attended Pacifica High School in Garden Grove, California, where he graduated as class valedictorian in 1984. During high school, Holland was the best student in mathematics in his year, and he found it "just as exciting as punk rock." He then attended the University of Southern California, where he earned a B.S. degree in biology and an M.S. degree in molecular biology, and was a candidate for a Ph.D. in molecular biology. However, after the success of The Offspring, he suspended his studies to focus on music. In an interview in 1995, Holland had said when he turns 40, he would rather be a professor at a university than play music.
Holland's early influences include Aerosmith, The Beatles, the Sex Pistols, the Ramones, KISS, Bob Marley, Queen, and The Rolling Stones. After he met friend and cross-country teammate Greg K., they started a local punk band called Manic Subsidal in 1984, where he played the drums. It formed after the duo failed to get into a Social Distortion concert. After Jim Benton was hired as their drummer, Holland switched to both vocals and guitars. They never released any albums, but some demos have existed online.