As an undergraduate student, Mukasey was the editorials editor of the Columbia Daily Spectator at Columbia University, where he received his B.A. in 1963. At Yale Law School he received his LL.B. in 1967. Mukasey practiced law for 20 years in New York City, serving for four years as an Assistant United States Attorney in the federal prosecutor's office in which he worked with Rudolph Giuliani. In 1976, he joined the New York law firm of Patterson Belknap Webb & Tyler, to which he returned after retirement from the U.S. District Court. Mukasey began teaching at Columbia Law School in the Spring of 1993 and has taught there every spring semester since.
Mukasey's son Marc L. Mukasey, as of 2007, leads the white-collar criminal defense practice in the New York office of Bracewell & Giuliani. The Mukaseys have a professional relationship with Rudy Giuliani; Mukasey and son were also justice advisers to Rudy Giuliani's presidential campaign. Mukasey administered the oath of office to Mayor-elect Giuliani in 1994 and 1998.
During his tenure on the bench, Mukasey presided over the criminal prosecution of Omar Abdel Rahman and El Sayyid Nosair, whom he sentenced to life in prison for a plot to blow up the United Nations and other Manhattan landmarks uncovered during an investigation into the 1993 World Trade Center bombing. During that case, Mukasey spoke out against leaks by law enforcement officials regarding the facts of the case allegedly aimed at prejudicing potential jurors against the defendants.
Mukasey also heard the trial of Jose Padilla, ruling that the U.S. citizen and alleged terrorist could be held as an enemy combatant but was entitled to see his lawyers. Mukasey also was the judge in the litigation between developer Larry Silverstein and several insurance companies arising from the destruction of the World Trade Center. In a 2003 suit, he issued a preliminary injunction preventing the Motion Picture Association of America from enforcing its ban against the distribution of screener copies of films during awards season, ruling that the ban was likely an unlawful restraint of trade unfair to independent filmmakers.
In June 2003, Democratic New York Senator Charles Schumer submitted Mukasey's name, along with four other Republicans or Republican appointees, as a suggestion for Bush to consider for nomination to the Supreme Court.
On October 14, 2004, citing U.S. Supreme Court precedent, Mukasey reversed his September 2002 decision and dismissed a case in which plaintiffs in twenty consolidated actions sued the Italian insurance company Generali S.p.A. (Generali), seeking damages for nonpayment of insurance proceeds to beneficiaries of policies purchased by Holocaust victims before the end of World War II. In so ruling, Mukasey gave deference to "a federal executive branch policy favoring voluntary resolution of Holocaust-era insurance claims.
Since retiring from the bench, Mukasey made campaign contributions to Giuliani for president and Joe Lieberman for Senate. Mukasey was also listed on the Giuliani campaign's Justice Advisory Committee.
On August 22 2007, the Wall Street Journal published Mukasey's op-ed, prompted by the resolution of the Padilla prosecution, in which he argued that "current institutions and statutes are not well suited to even the limited task of supplementing . . . a military effort to combat Islamic terrorism." Mukasey instead advocated for Congress, which "has the constitutional authority to establish additional inferior courts," to "turn [its] considerable talents to deliberating how to fix a strained and mismatched legal system.
White House spokeswoman Dana Perino said on September 18 that the administration desired the Mukasey nomination be confirmed by October 8 2007. She cited past prompt confirmations of attorneys general. Senator Patrick Leahy, the Democratic Chairman of the Senate Judiciary Committee, said that Mukasey would commit to an administrative rule to ensure that only the Attorney General or Deputy Attorney General, not U.S. Attorneys or other Justice employees, could respond to inquiries from politicians regarding outstanding cases, and that any other employee who discusses cases "with somebody outside, whether from the White House or members of Congress or something else like that, they will be fired"; this concession sought to avoid problems that arose during the controversy over the dismissal of U.S. Attorneys under the previous Attorney General's tenure.
On October 2 2007 Mukasey's written response to a pre-hearing Senate Judiciary Committee questionnaire was received by the committee, and published. Leahy replied the next day by letter proposing to meet individually on October 16, to discuss numerous issues on which the White House has declined to respond; the letter outlined issues and commitments Leahy desires from the nominee. On November 6 the Senate Judiciary Committee endorsed the nomination of Mukasey, by a 11 to 8 vote, and sent his confirmation on to the full Senate. Two days later, the Senate confirmed Mukasey by a 53–40 vote. The tight vote was the narrowest margin to confirm an attorney general in more than 50 years.
Mukasey was sworn in at a private ceremony on November 9.
Senator Leahy announced on October 31 2007 that a committee vote on the nomination was scheduled for Tuesday, November 6. The announcement came a day after Mukasey replied via letter to the committee, to questions and requests for clarification. Leahy and the other nine Democratic committee members had indicated the week before, via letter, to Mukasey that they were "deeply troubled by your refusal to state unequivocally that waterboarding is illegal during your confirmation hearing... By holding an unusual Oval Office meeting with journalists on November 1, 2007, Bush signaled his concern that the nomination, which was previously judged to be a sure bet, was in peril, primarily over what is and is not considered illegal torture. Mukasey has refused to state an unequivocal legal position on the interrogation technique known as waterboarding (in which water is poured over a rag on the prisoner's face to simulate drowning), and it appears that he was concerned about the potential pursuit of government employees or agents, and their authorizing superiors in American or foreign courts under criminal charges, when responding to the Senate Judiciary committee questions.
In describing the issue's challenges to the Bush administration, the New York Times quoted Scott L. Silliman, director of the Center on Law, Ethics and National Security at Duke University as saying about such court cases, which could ultimately reach the president: "You would ask not just who carried it out, but who specifically approved it." Robert M. Chesney, of Wake Forest University School of Law, and other national security specialists have pointed out that prosecution within the United States, would be impeded by laws adopted since 2005 which permit safe-harbor protections to interrogators for governmentally authorized actions. It is believed that secret Justice Department legal opinions approved waterboarding, and other harsh interrogation techniques.
Mukasey's son, Marc Mukasey, has been assigned by Giuliani's campaign to block Kerik's legal defense team from interviewing witnesses that might assist his defense.
On August 12, 2008 Mukasey told American Bar Association annual meeting delegates that "not every wrong, or even every violation of the law, is a crime", with "only violations of the civil service laws" being found among hiring practices during Gonzales' tenure as Attorney General.