The Eugenics Record Office (ERO) was founded at Cold Spring Harbor, New York, by Davenport with initial support from Mary Williamson Averell (Mrs. E. H. Harriman) and John Harvey Kellogg, and later by the Carnegie Institution of Washington. Laughlin was made the managing director and was zealous in pursuing the goals of the institution, even co-writing a eugenical comedy in four acts for performance at the ERO for the amusement of the field workers being trained, and he regularly lectured to various groups around the country. In 1917 he earned a Doctor of Science from Princeton University in the field of cytology.
Laughlin provided extensive statistical testimony to the United States Congress in support of the Johnson-Reed Immigration Act of 1924. Part of his testimony dealt with "excessive" insanity among immigrants from southern Europe and eastern Europe. He was eventually appointed as an expert eugenics agent to the Committee on Immigration and Naturalization. (The 1924 law applied national-origin quotas on immigrants which stopped the large Italian and Russian influx of the early 1900s). At least one contemporary scientist, bacterial geneticist Herbert Spencer Jennings, condemned Laughlin's statistics as invalid due to the comparison of recent immigrants to more settled immigrants. In 1927 the Eugenics Research Association, of which Laughlin was an officer, began a study of the heritage of U.S. Senators. Some senators were enthusiastic, others reluctantly complied, while Senator William Cabell Bruce questioned whether eugenics was even a science and refused to participate. Nonplused, Laughlin wrote to Bruce's hometown newspaper in an attempt to get the information.
One of Laughlin's key interests was to aid in the proliferation of compulsory sterilization legislation in the United States, which would presumably sterilize the "unfit" members of the population. By 1914, 12 states had already passed sterilization laws, beginning with Indiana in 1907 and Connecticut in 1909, however in most states the laws were not employed with significant vigor (California was the sole exception to this). In his study of this "problem," Laughlin deduced that much of the state sterilization legislation was poorly worded and left it open to questions of constitutionality and confusion over bureaucratic responsibility. As a result, Laughlin drafted a "model law" for compulsory sterilization which would satisfy these difficulties, and published them in his 1922 study of American sterilization policy, Eugenical Sterilization in the United States. It included as subjects for eugenic sterilization: the feeble minded, the insane, criminals, epileptics, alcoholics, blind persons, deaf persons, deformed persons, and indigent persons. An additional 18 states passed laws based on Laughlin's model, including Virginia in 1924. The first person ordered sterilized in Virginia under the new law was Carrie Buck, on the grounds that she was the "probable potential parent of socially inadequate offspring". A lawsuit ensued and Laughlin, who had never met Buck, gave a deposition endorsing her suitability for sterilization, calling the family members of “the shiftless, ignorant, and worthless class of anti-social whites of the South”. Other scientists from the ERO testified in person. The state won the case, which was appealed to the United States Supreme Court in 1927. The resulting case, Buck v. Bell, upheld the constitutionality of the laws that Laughlin helped write. Five months after the court confirmed the law Carrie Buck was sterilized. (A law allowing for the sterilization of repeat criminals was overturned in 1942, in Skinner v. Oklahoma, but sterilizations of mental patients continued into the 1970s. Altogether, more than 60,000 Americans were sterilized. Virginia repealed its sterilization law in 1974). Laughlin also supported the passage of Virginia's Racial Integrity Act, which outlawed miscegenation. (That law was overturned by the US Supreme Court in Loving v. Virginia in 1967).
The Reichstag of Nazi Germany passed the Law for the Prevention of Hereditarily Diseased Offspring in 1933, loosely based on Laughlin's model. Between 35,000 and 80,000 persons were sterilized in the first full year alone. (It is now known that over 350,000 persons were sterilized). Laughlin was awarded an honorary degree by the University of Heidelberg in 1936 for his work behalf of the “science of racial cleansing.” (Five other Americans received honorary degrees the same year). However, reports about the extensive use of compulsory sterilization in Germany began to appear in US newspapers. By the end of the decade, eugenics had become associated with Nazism and poor science. Support for groups like the American Eugenics Society began to fade. In 1935, a review panel convened by the Carnegie Institute concluded that the ERO's research did not have scientific merit. By 1939, the Institute withdrew funding for the ERO, and the office was forced to close.
Laughlin was a founding member of the Pioneer Fund, and was its first president, serving from 1937 to 1941. The Pioneer Fund was created by Wickliffe Draper in order to promote the betterment of the race through eugenics. Draper had been supporting the Eugenics Research Association and its Eugenical News since 1932. One of the first projects that Laughlin pursued for the Fund was the distribution of two films from Germany depicting the success of eugenic programs in that country.
Laughlin himself eventually discovered that he suffered from epilepsy, which was one of the subjects of study at the ERO and one of the criterion for compulsory sterilization under his own law. He and his wife, Pansy, married in 1902, but never had any children. After the ERO closed he returned in 1939 to Iowa, where he resided until his death.