Spence graduated from the University of Wyoming in 1949 and from the University of Wyoming College of Law in 1952. He was awarded an honorary Doctor of Laws degree in May 1990. He started his career in Riverton, Wyoming, and later became a successful defense attorney for the insurance industry. Years later, Spence said he “saw the light” and became committed to representing people instead of corporations, insurance companies, banks, or “big business”.

From 1954 to 1962 he served as Prosecuting Attorney of Fremont County, Wyoming.

Spence gained attention for the Karen Silkwood case. Karen Silkwood was a chemical technician at the Kerr-McGee plutonium-production plant, where she became an activist and vocal critic of plant safety, also known as a whistleblower. On November 13, 1974, Silkwood died in a one-car crash under suspicious circumstances after reportedly gathering evidence for her union. Spence represented Silkwood’s father and children, who charged that Kerr-McGee was responsible for exposing Silkwood to dangerous levels of radiation. Spence won a $10.5 million verdict for the family.

In 1984, the Supreme Court of the United States upheld the family’s right to sue under state law for punitive damages from a federally regulated industry. The Silkwood case achieved international fame and was the subject of many books, magazine and newspaper articles and the major motion picture Silkwood starring Meryl Streep as Karen Silkwood.

After the Silkwood case, Spence tried a number of high-profile cases. He has not lost a civil case since 1969 and has never lost a criminal case with a trial by jury. He has had several of his more prominent civil verdicts overturned on appeal and lost a 1985 manslaughter case in a bench trial in Newport, Oregon, in December 1985, later prevailing on appeal.

In 1986, Spence defended Lee Harvey Oswald, the deceased assassin of U.S. President John F. Kennedy, against well-known prosecutor Vincent Bugliosi in a 21-hour televised unscripted mock trial sponsored by London Weekend Television in the United Kingdom. The mock trial involved an actual U.S. judge, a jury of U.S. citizens, the introduction of hundreds of evidence exhibits, and many actual witnesses to events surrounding and including the assassination. The jury returned a guilty verdict. Expressing admiration for his adversary’s prosecutorial skill, Spence remarked, “No other lawyer in America could have done what Vince did in this case.” The “docu-trial” and his preparation for it inspired Bugliosi’s 1600-page book examining the details of the Kennedy assassination and various related conspiracy theories, entitled Reclaiming History, winner of the 2008 Edgar Award for Best Fact Crime. Several times in the book Bugliosi specifically cites his respect for Spence’s abilities as a defense attorney as his impetus for digging more deeply into various aspects of the case than he perhaps would have otherwise.

Spence also defended Earth First! founder David Foreman, who in 1990 had been charged with conspiracy for an alleged plot to sabotage a water-pumping station.

In civil litigation, Spence won a $52 million verdict against McDonald’s Corporation on behalf of a small, family-owned ice cream company. A medical malpractice verdict of over $4 million established a new standard for nursing care in Utah. In 1992 Spence earned $33.5 million verdicts for emotional and punitive damages for his quadriplegic client after a major insurance company refused to pay on the $50,000 policy.

On June 2, 2008, Spence obtained an acquittal of Detroit lawyer Geoffrey Fieger, who was charged with making unlawful campaign contributions. Before returning a not-guilty verdict, the federal court jury deliberated 18 hours over four days. The acquittal kept Spence’s record of never having lost a criminal case intact.

After winning the Fieger acquittal in 2008, Spence told jurors, “This is my last case. I will be 80 in January, and it’s time for me to quit, to put down the sword.” In 2010, Spence was still listed as an active partner in the Spence Law Firm, located in Jackson, Wyoming, and continues to make public appearances. Gerry Spence’s next case, a civil suit for wrongful incarceration, ended with a mistrial in December 2012, when the jury could not come to a unanimous decision. Per the cite to the AP story : “The verdicts Pratt read in court indicated jurors had found in favor of Larsen, Brown and the city of Council Bluffs on both major issues. The first issue was whether Harrington and McGhee’s constitutional rights to due process had been violated. The second was whether the city had failed to adequately train and supervise the police officers. When the judge polled the jurors to ensure all agreed, three women said no.” In October 2013, the AP reported that the suit was settled between the two parties four days before a retrial was scheduled to start.