He has been an adjunct professor of public health at Columbia University Medical School and is a member of the Institute of Medicine of the National Academy of Sciences.

He was commissioned an ensign in November 1955, served three years in the Office of the Judge Advocate General in Washington, D.C., and was released to inactive duty in October 1958, as a lieutenant.

Subsequently, he was also selected to present the United States case before the International Commission of Jurists during hearings held in Panama dealing with those riots.

He also worked on a variety of domestic problems, including labor-management relations, balance of payments, health care, education, environmental and urban issues, and civil rights.

He put the department through the most complete reorganization in its twenty-five year history; created the Health Care Financing Administration (HCFA) to run Medicare and Medicaid; mounted major health promotion and disease prevention programs, including childhood immunization, the first national anti-smoking campaign, an alcoholism initiative, and issuance of Healthy People, the initial Surgeon General's Report on Health Promotion and Disease Prevention which for the first time set health goals for the American people; began the collection of hundreds of millions of dollars of defaulted student loans, and instituted computerized techniques to police welfare, Medicare and Medicaid programs; worked with the Congress to maintain the financial integrity of the Social Security system, contain health care costs, and restructure Federal aid to elementary, secondary and higher education; and issued the first regulations to provide equal athletic opportunity to women under Title IX and to provide equal opportunity to the handicapped.

As Secretary, Califano opposed the Burger Court's Regents of the University of California v. Bakke decision limiting affirmative action and pressed the Carter administration to administer stronger desegregation policies.

[8] However, initially he refused to sign meaningful regulations for Section 504 of the Rehabilitation Act of 1973, which was the first U.S. federal civil rights protection for people with disabilities.

This sit-in, led by Judith Heumann and organized by Kitty Cone, lasted until April 30, 1977, 25 days, with more than 150 people refusing to leave.

In 1979, as Secretary, Califano directed the Public Health Service to eliminate its official characterization of homosexuality as "a mental disease or defect" which immigration authorities had used to deny individuals entry to the United States solely because of their sexual orientation.

In 1979, Califano led a United States delegation to China on a trip which resulted in long-term institutionalization of health and education links between the two countries.

He was Founding Chairman of the Board of the Institute for Social and Economic Policy in the Middle East at the John F. Kennedy School of Government at Harvard University.

In 2010, Califano received the Gustav O. Lienhard Award from the Institute of Medicine for his contributions to improving public health, his leadership in catalyzing federal action to curb smoking and his broader efforts to reduce the toll of addiction and substance abuse.

His third, The Media and the Law, was published by Praeger Special Studies in 1976 and was co-authored and co-edited with Howard Simons, Managing Editor of The Washington Post.

In May 1981, Simon and Schuster published Califano's fifth book, Governing America: An Insider's Report from the White House and the Cabinet, about his years as Secretary of HEW.

His eighth book, The Triumph and Tragedy of Lyndon Johnson: The White House Years, was published by Simon and Schuster in 1991 and republished by Texas A & M University Press in 2000.