After the Supreme Court’s 1954 Brown vs. Board of Education decision, Jesse Helms’s Tarheel Banker editorials took on a racial slant unique for a banking trade magazine. Helms consistently linked integration efforts with communism. In 1957, as federal troops escorted the first black students inside Little Rock High School, Helms wrote,"What is happening in America is exactly in tune with the forecast of Karl Marx...The cackles you hear have a Russian accent."

"I thought it very unwise, and it was taking liberties away from one group of citizens and giving them to another. I thought it was bad legislation then and I have had nothing to change my mind about it."   – Jesse Helms

In the 1960s, Jesse Helms became known in certain circles as the "media master" of conservative viewpoints opposing the civil rights movement and its impassioned leader, Martin Luther King, Jr. In a 1963 WRAL-TV "Viewpoint" editorial, Helms said, "Dr. King's outfit…is heavily laden at the top with leaders of proven records of communism, socialism and sex perversion, as well as other curious behavior." He called the Civil Rights Act of 1964 "the single most dangerous piece of legislation ever introduced in the Congress."

"The abortion question came up shortly after I came to the Senate. The Supreme Court decision came down. That sort of thing got me started in trying to make some changes in the way the country feels about various things." 
– Jesse Helms

Known as "Senator No" for his consistent efforts to block what he considered liberal initiatives and unqualified foreign policy appointees, Jesse Helms repeatedly introduced bills seeking to overturn the 1973 Roe v. Wade decision legalizing abortion.

As Helms’s 1990 bid for reelection approached, he knew foreign relations would not be his ticket to a fourth term. He needed a domestic issue to mobilize his conservative base, just as his opposition to the King holiday had six years earlier. Helms pounced on the National Endowment for the Arts for supporting the work of artists like Andres Serrano, who photographed a crucifix in urine, and Robert Mapplethorpe, whose photographs included homoerotic images. Helms proposed an amendment to prevent the NEA from sponsoring “obscene or indecent” art, provoking widespread outcries of censorship.

In June of 1995, Patsy Clarke, whose late husband had been a consultant to Helms and whose son died of AIDS in 1994, read in a newspaper that Helms felt AIDS sufferers deserve their fate because HIV is spread through what he called "risky behavior." Clarke was inspired to write Helms, and in his reply to Clarke, he wrote, "As for homosexuality, the Bible judges it, I do not…. I understand the militant homosexuals and they understand me. They climbed onto the roof of Dot’s and my home and hoisted a giant canvas condom…. As for Mark, I wish he had not played Russian roulette in his sexual activity." Two weeks after writing Clarke, Helms blocked renewal of the Ryan White Care Act, a health care program for AIDS victims named for the late Indiana teenager who acquired the virus from a blood transfusion. The disease, Helms said, is the result of "deliberate, disgusting, revolting conduct." Clarke, who had always voted for Jesse Helms, established MAJIC (Mothers Against Jesse in Congress) to oppose Helms’s bid for a fifth term in 1996.

"Each of us, all of our churches, must do something.  We dare not avert our eyes. In the name of Christ, for the sake of his kingdom, please help." - Jesse Helms’s 2005 World AIDS Day Appeal

In 2001, the Senator Helms, who once condemned foreign aid programs as "rat holes," agreed to a meeting to discuss AIDS relief funding with U2 singer and activist Bono. Helms later said he was ashamed of the way he had felt about the AIDS pandemic and proposed a $500 million emergency appropriation for global AIDS relief.