The clinic was named for French Marxist physician Paul Lafargue and conceived by German-American psychiatrist Fredric Wertham, who recognized the dire state of mental health services for blacks in New York.

With the backing of black intellectuals Richard Wright and Ralph Ellison, as well as members of the church and community, the clinic operated out of the parish house basement of St. Philip's Episcopal Church and was among the first to provide low-cost psychiatric health services to the poor, especially for poor blacks who either could not afford treatment at New York hospitals or faced racial discrimination from doctors and other hospital staff.

Wertham would use case studies from his time at the clinic to support his later arguments that comic books caused juvenile delinquency, as evidenced in his 1954 work Seduction of the Innocent.

In September 1946, after the establishment of the clinic, Wright penned an article in Free World titled Psychiatry Comes to Harlem, where he described the destitute state of mental health services for blacks in New York: "[T]hat Harlem's 400,000 black people produced 53% of all the juvenile delinquents of Manhattan, which has a white population of 1,600,000; that, while in theory Negroes have access to psychiatric aid (just as the Negroes of Mississippi, in theory, have access to the vote!

"[5] Wertham also unsuccessfully petitioned mayor Fiorello H. La Guardia to create preventive psychiatry facilities in Harlem for at least ten years, adding to his frustration with the city's treatment of black mental patients.

[7] The clinic, which the men named after French Marxist physician Paul Lafargue, opened on March 8, 1946, and served patients from 6 to 8 o'clock on Tuesdays and Thursdays.

According to Dennis Doyle, a medical historian and expert on Lafargue, demand was so great for services that "the waiting list was still full in the clinic's final years".

[9] The clinic saw around 70% adults and 30% children (other progressive psychiatrists opened another Harlem facility in 1946 called the Northside Center, which primarily served children), and operated under what Doyle referred to as a combination of "race-blind universalism" (which meant that doctors did not, as was common practice at the time, make adjustments in their diagnoses for biological conceptions of race) and social psychiatry, at that time a new clinical approach.

And here, finally, are the social workers at the reception desks; and there, waiting upon the benches rowed beneath the pipes carrying warmth and water to the floors above, are the patients.

[13] When doctors at Lafargue made a diagnosis of a serious brain disease, they referred their patients to outside hospitals, providing blacks a pathway to proper medical care.

His replacement, a Columbia University graduate named M. Moran Weston, turned the parish house into a center for community services and health programs headed by members of the St. Philip's congregation.

Best typified by his 1954 book Seduction of the Innocent, which claimed that comics were pathological and negative influences on children, many of Wertham's case studies and anecdotal references came from his time at Lafargue and at Queens General Hospital.

[23] In the early 1950s, the NAACP Legal Defense and Educational Fund (LDEF) began to seek more authoritative scientific evidence that Jim Crow schools were detrimental to black children.

[24] The LDEF successfully challenged segregation in higher education in Sweatt v. Painter and McLaurin v. Oklahoma State Regents, but now looked towards overturning the doctrine of separate but equal, which was still in effect from Plessy v. Ferguson.

[30] Medical historian Dennis Doyle wrote favorably of the clinic, that it resulted from a "complex interaction" of community persons, Harlem leaders, and progressive psychiatrists.