Morrell began work as an English professor at the University of Iowa in 1970. In 1972, his novel First Blood was published; it would eventually be made into the 1982 film of the same name starring Sylvester Stallone as Vietnam veteran John Rambo. Morrell continued to write many other novels, including The Brotherhood of the Rose, the first in a trilogy of novels, which was adapted into a 1989 NBC miniseries starring Robert Mitchum. Eventually tiring of the two professions, he gave up his tenure at the university in 1986 in order to write full time.

Morrell's teenaged son Matthew died of Ewing's Sarcoma, a rare form of bone cancer in 1987. The trauma of his loss influenced Morrell's work, in particular in his exciting creative fiction memoir about Matthew, Fireflies. The protagonist of Morrell's novel Desperate Measures also experiences the loss of a son.

Morrell is the co-president of the International Thriller Writers organization.

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