Wolpe grew up in South Africa, attending Parktown Boys' High School and obtaining his MD from the University of the Witwatersrand.

In 1956, Wolpe was awarded a Ford Fellowship and spent a year at Stanford University in the Center for Behavioral Sciences, subsequently returning to South Africa but permanently moving to the United States in 1960 when he accepted a position at the University of Virginia.

[1][2] One of the most influential experiences in Wolpe's life was when he enlisted in the South African army as a medical officer.

Wolpe was entrusted to treat soldiers who were diagnosed with what was then called "war neurosis" but today is known as post traumatic stress disorder.

The mainstream treatment of the time for soldiers was based on psychoanalytic theory, and involved exploring the trauma while taking a hypnotic agent – so-called narcotherapy.

In Wolpe's search for a more effective way in treating anxiety he developed different reciprocal inhibition techniques, utilizing assertiveness training.

[9] This idea was not necessarily original to Wolpe as a similar concept was discussed in works of Abu Zayd al-Balkhi, who lived about 1000 years earlier.

There are three main steps in using systematic desensitization, following development of a proper case formulation[12] or what Wolpe originally called, "behavior analysis".

Furthermore, Wolpe was a prolific writer, some of his most famous books include, The Practice of Behavior Therapy and Psychotherapy by Reciprocal Inhibition.

He also created the Subjective Anxiety Scale (SAS) and the Fear Survey Plan that are used in behavior research and therapy.