Skinner received a PhD from Harvard in 1931, and remained there as a researcher until 1936. He then taught at the University of Minnesota at Minneapolis and later at Indiana University, where he was chair of the psychology department from 1946–1947, before returning to Harvard as a tenured professor in 1948. He remained at Harvard for the rest of his life. In 1973, Skinner was one of the signers of the Humanist Manifesto II.

In 1936, Skinner married Yvonne (Eve) Blue. The couple had two daughters, Julie (m. Vargas) and Deborah (m. Buzan). Yvonne Skinner died in 1997, and is buried in Mount Auburn Cemetery, Cambridge, Massachusetts.

Reinforcement, a key concept of behaviorism, is the primary process that shapes and controls behavior, and occurs in two ways, "positive" and "negative." In The Behavior of Organisms (1938), Skinner defined "negative reinforcement" to be synonymous with punishment, that is, the presentation of an aversive stimulus. Subsequently, in Science and Human Behavior (1953), Skinner redefined negative reinforcement. In what has now become the standard set of definitions, positive reinforcement is the strengthening of behavior by the occurrence of some event (e.g., praise after some behavior is performed), whereas negative reinforcement is the strengthening of behavior by the removal or avoidance of some aversive event (e.g., opening and raising an umbrella over your head on a rainy day is reinforced by the cessation of rain falling on you).

Skinner is popularly known mainly for his books Walden Two and Beyond Freedom and Dignity, (for which he made the cover of TIME Magazine). The former describes a fictional "experimental community" in 1940s United States. The productivity and happiness of citizens in this community is far greater than in the outside world because the residents practice scientific social planning and use operant conditioning in raising their children.

To strengthen behavior, Skinner used operant conditioning, and he considered the rate of response to be the most effective measure of response strength. To study operant conditioning, he invented the operant conditioning chamber, also known as the Skinner Box, and to measure rate he invented the cumulative recorder. Using these tools, he and C. B. Ferster produced his most influential experimental work, which appeared in their book Schedules of Reinforcement (1957).

Walden Two, like Thoreau's Walden, champions a lifestyle that does not support war, or foster competition and social strife. It encourages a lifestyle of minimal consumption, rich social relationships, personal happiness, satisfying work, and leisure. In 1967, Kat Kinkade and others founded the Twin Oaks Community, using Walden Two as a blueprint. The community still exists and continues to use the Planner-Manager system and other aspects of the community described in Skinner's book, though behavior modification is not a community practice.

Modern behavioral Psychologists have disputed Skinner's "superstition" explanation for the behaviors he recorded. Subsequent research (e.g. Staddon and Simmelhag, 1971), while finding similar behavior, failed to find support for Skinner's "adventitious reinforcement" explanation for it. By looking at the timing of different behaviors within the interval, Staddon and Simmelhag were able to distinguish two classes of behavior: the terminal response, which occurred in anticipation of food, and interim responses, that occurred earlier in the interfood interval and were rarely contiguous with food. Terminal responses seem to reflect classical (as opposed to operant) conditioning, rather than adventitious reinforcement, guided by a process like that observed in 1968 by Brown and Jenkins in their "autoshaping" procedures. The causation of interim activities (such as the schedule-induced polydipsia seen in a similar situation with rats) also cannot be traced to adventitious reinforcement and its details are still obscure (Staddon, 1977).

Writing in 1981, Skinner pointed out that Darwinian natural selection is, like reinforced behavior, "selection by consequences." Though, as he said, natural selection has now "made its case", he regretted that essentially the same process, "reinforcement", was less widely accepted as underlying human behavior.

Skinner’s public exposure had increased in the 1970s, he remained active even after his retirement in 1974, until his death. In 1989, Skinner was diagnosed with leukemia and died on August 18, 1990 in Cambridge, Massachusetts. Ten days before his death, he was given the lifetime achievement award by the American Psychological Association and gave a talk in an auditorium concerning his work.

A 2004 book by Lauren Slater, entitled Opening Skinner's Box: Great Psychology Experiments of the Twentieth Century caused a stir by mentioning the rumors that Skinner had used his baby daughter, Deborah, in some of his experiments, and that she had subsequently committed suicide. Although Slater's book stated that the rumors were false, a reviewer in The Observer in March 2004 misquoted Slater's book as supporting the rumors. This review was read by Deborah Skinner (now Deborah Buzan, an Artist and Writer living in London) who wrote a vehement riposte in The Guardian.

Skinner's book, Walden Two, presents a vision of a decentralized, localized society, which applies a practical, scientific approach and behavioral expertise to deal peacefully with social problems. (For Example, his views led him to oppose corporal punishment in schools, and he wrote a letter to the California Senate that helped lead it to a ban on spanking.) Skinner's utopia is both a thought experiment and a rhetorical piece. In Walden Two, Skinner answers the Problem that exists in many utopian novels – "What is the Good Life?" The book's answer is a life of friendship, health, art, a healthy balance between work and leisure, a minimum of unpleasantness, and a feeling that one has made worthwhile contributions to a society in which resources are ensured, in part, by minimizing consumption.

As understood by Skinner, ascribing dignity to individuals involves giving them credit for their actions. To say "Skinner is brilliant" means that Skinner is an originating force. If Skinner's determinist theory is right, he is merely the focus of his environment. He is not an originating force and he had no choice in saying the things he said or doing the things he did. Skinner's environment and genetics both allowed and compelled him to write his book. Similarly, the environment and genetic potentials of the advocates of freedom and dignity cause them to resist the reality that their own activities are deterministically grounded. J. E. R. Staddon (The New Behaviorism, 2nd Edition, 2014) has argued the compatibilist position; Skinner's determinism is not in any way contradictory to traditional notions of reward and punishment, as he believed.

He attended Hamilton College in New York with the intention of becoming a Writer. He found himself at a social disadvantage at Hamilton College because of his intellectual attitude. While attending, he joined Lambda Chi Alpha fraternity. Hamilton was known for being a strong fraternity college. Skinner had thought that his fraternity brothers were respectful and did not haze or mistreat the newcomers, instead, they helped out the other boys with courses or other activities. Freshman were called “‘slimers’” who had to wear small green knit hats and greet everyone that they passed for punishment. The year before Skinner entered Hamilton, there was a hazing accident that caused the death of a student. The freshman was asleep in his bed when he was pushed onto the floor, where he smashed his head, and resulting in his death. Skinner had a similar incident where two freshmen captured him and tied him to a pole, where he should have stayed all night, but he had a razor blade in his shoe for emergency and managed to cut himself free. He wrote for the school paper, but, as an atheist, he was critical of the traditional mores of his college. After receiving his Bachelor of Arts in English literature in 1926, he attended Harvard University, where he would later research, teach, and eventually become a prestigious board member. While he was at Harvard, a fellow student, Fred Keller, convinced Skinner that he could make an experimental science from the study of behavior. This led Skinner to invent his prototype for the Skinner Box and to join Keller in the creation of other tools for small experiments. After graduation, he unsuccessfully tried to write a great novel while he lived with his parents, a period that he later called the Dark Years. He became disillusioned with his literary skills despite encouragement from the renowned poet Robert Frost, concluding that he had little world experience and no strong personal perspective from which to write. His encounter with John B. Watson's Behaviorism led him into graduate study in psychology and to the development of his own version of behaviorism.

Skinner's views influenced education as well as psychology. Skinner argued that education has two major purposes: (1) to teach repertoires of both Verbal and nonverbal behavior; and (2) to interest students in learning. He recommended bringing students’ behavior under appropriate control by providing reinforcement only in the presence of stimuli relevant to the learning task. Because he believed that human behavior can be affected by small consequences, something as simple as "the opportunity to move forward after completing one stage of an activity" can be an effective reinforcer . Skinner was convinced that, to learn, a student must engage in behavior, and not just passively receive information. (Skinner, 1961, p. 389).