Thompson told FOX News Sunday in March 2007 that he is "pro-life," and that he believes Roe v. Wade was based on "bad law and bad medical science" that could be remedied through the appointment of "good judges." At the October 2007 Values Voter Summit, Thompson said that seeing the sonogram of his daughter solidified his anti-abortion stance, and added that as a result, "no legislation will pass my desk that funds or supports this procedure without my veto." While serving in the Senate he voted for the Partial-Birth Abortion Act of 2000. On a 1996 Christian Coalition survey, he handwrote, "I do not believe abortion should be criminalized. This battle will be won in the hearts and souls of the American people." In a 1994 political questionnaire Thompson indicated that he agreed with the statement "abortions should be legal in all circumstances as long as the procedure is completed within the first trimester of the pregnancy." 

Thompson has criticized the judiciary for overstepping its bounds and attempting to set "social policy." He wrote that "Many federal judges seem intent on eliminating God from the public schools and the public square in ways that would astound our founding fathers. … They ignore the fact that the founders were protecting the church from the state and not the other way around." 

Thompson has said that while "the use of DNA evidence to clear long-held prisoners from murder charges proves that we need to be more careful about handing out death sentences," scientific studies have shown "that the death penalty deters murders." Thompson voted for a 1996 bill to limit death penalty appeals. In a 1994 political questionnaire, Thompson indicated support for "impos[ing] the death penalty for certain federal crimes, including civil rights murders, rape and child molestation murders, death resulting from drive-by shootings or carjacking, and murder of court officers or federal witnesses." 

In 2001 he voted against increasing tax credits for college tuition and student loan payments, though in 2000 he voted in favor of allowing parents to create tax-free savings accounts for educational expenses. In 1997 he voted for a bill to allow school vouchers in the District of Columbia and again supported vouchers in a 1999 vote. In 1996 he voted in favor of federally funded abstinence education for high school students. 

Speaking on his ABC Radio show, Thompson questioned the idea of global warming, pointing to evidence of warming on other planets in the solar system: "This has led some people, not necessarily scientists, to wonder if Mars and Jupiter, non-signatories to the Kyoto Treaty, are actually inhabited by alien SUV-driving industrialists who run their air-conditioning at 60 degrees and refuse to recycle." He has since said that "climate change is real." In 1999 he voted against an amendment to increase federal funding for solar and renewable energy programs and against allowing the study of tougher fuel efficiency standards. 

As a senator, Thompson supported President Bush's Faith-Based Initiative, writing in 2001 that "we should stop spending billions of dollars on programs we don't know are working and allow faith-based programs to compete for this funding." 

Thompson said he believes Americans should be "a tolerant people" but added that he opposes "special rights" for anyone. He said that "Marriage is between a man and a woman, and I don't believe judges ought to come along and change that." During the October 2007 Values Voter Summit, Thompson appeared to support a constitutional amendment defining marriage as between a man and a woman. In March 2007, he said that states should have "great leeway" in deciding whether to allow civil unions between gay partners. In 2000 he voted against expanding federal hate crime protections to include gender, sexual orientation and disability. 

Thompson has criticized "socialized medicine" proposals, saying that national health care systems in Canada and England are "coming apart at the seams." He supports President Bush's call for electronic medical record keeping to save money, reduce medical errors and keep insurance premiums down. In 2001 Thompson voted against a bill allowing patients to sue health insurance providers. In 1998 he voted against increasing tobacco restrictions, and in 1996 he voted against health care savings accounts. 

Thompson said there is "no good solution" to the problem of illegal immigration but that border enforcement must come before any other legislation. He criticized Mexican President Philipe Calderon's leftist economic policies for contributing to illegal immigration. While he was a member of the Senate, Thompson voted to allow more temporary immigrant workers and more highly skilled immigrants. He also voted to limit welfare benefits for legal immigrants. In October 2007, Thompson announced that he would crack down on cities and other areas that provide sanctuaries and social services for illegal immigrants. 

Thompson said in March 2007 that he would do "essentially what the president's doing" on Iraq, though he noted that mistakes have to be "rectified." He said he has "faith" in General David Petraeus' leadership: "We need to take advantage of any opportunity we've got down there." If the U.S. pulls out of Iraq under "bad circumstances," Thompson warned, then Iraq will become a "haven for terrorists" and the resulting instability could lead Sunni countries to develop nuclear weapons as a counterweight to Iran's nuclear program. In an October 2007 interview, however, Thompson said that a long-term U.S. presence in Iraq "would not be a good development." When asked how he would define success in Iraq, he answered, "The average person being able to go to worship without fear of being blown up. ... Political leaders being able to meet without fear of being blown up. The key is stability, and that would signal a level of stability we haven't had." 

Thompson criticized programs that would "redistribute the income among our citizens" as "defeatist" in May 2007. A policy of lowering taxes, he said, would stimulate economic growth and "make the pie bigger." In 1999 he voted against an increase in the minimum wage. He also voted to reduce taxes on married couples in 2000. 

Thompson told the National Right to Life Conference in June 2007 that he supports adult stem-cell research, but not "stem-cell research where embryos of unborn children are destroyed." He said, "It looks to me like there is a lot of promising developments as far as adult stem-cell research is concerned anyway and we don't need to go down that other road."