In 1898 enrolling in the U.S. Army as a private, Dyer served notably in the Spanish–American War; and was promoted to Colonel at the war's end. Working as an attorney in St. Louis, Dyer started an anti-usury campaign and was elected to Congress as a Republican in 1910.

As a progressive reformer, Dyer authored an anti-usury law in 1914 that limited excessive loan rates by bank lenders in the nation's capital, then still governed by Congress.

In 1919, Dyer authored the motor-vehicle theft law, which made transporting stolen automobiles across state lines a federal crime. By 1956, the FBI reported that the law had enabled the recovery of cars worth more than $212 million.

In terms of Prohibition, Rep. Dyer voted against various anti-liquor laws, including the Eighteenth Amendment.

Horrified by the race riots in Saint Louis and East Saint Louis in 1917 and the high rate of reported lynchings in the South, in 1918 Dyer was notable for proposing the Dyer Anti-Lynching Bill. In 1920 the Republican Party supported such legislation in its platform from the National Convention. In January 1922, Dyer's bill was passed by the House, which approved it by a wide margin due to "insistent countrywide demand".

Dyer was distressed by such mob violence, with its disregard for the courts and the "rule of law". His district in St. Louis had mostly African-American residents and he wanted to protect his constituents and other citizens. Many people from his district had migrated to St. Louis from the South, in the exodus known as the Great Migration. They settled in St. Louis where industrialization had led to a strong economy and an increase in jobs. The economy had also attracted numerous immigrants from Europe and competition for work was high. Dyer also knew of the continuing high rate of lynchings, mostly of blacks by whites in the South. Working with W.E.B. DuBois and Walter White of the National Association for the Advancement of Colored People, who had been working on a national anti-lynching campaign, Dyer helped develop and agreed to sponsor anti-lynching legislation.

Calling for an end to mob violence, on April 1, 1918, Dyer introduced the Dyer Anti-Lynching Bill, which would have made lynching a federal crime. In his speech, he anticipated some members likely objections about the federal government sponsoring "social" legislation, and noted that lynching violated individuals' rights under the 14th Amendment. In addition, he noted that Congress had passed child labor laws and the Prohibition amendment. He said:

“If Congress has felt its duty to do these things, why should it not also assume jurisdiction and enact laws to protect the lives of citizens of the United States against lynch law and mob violence? Are the rights of property, or what a citizen shall drink, or the ages and conditions under which children shall work, any more important to the Nation than life itself?”

The first such federal legislation to gain House passage in the twentieth century, it would have enabled the federal government to prosecute the crime. Southern authorities seldom did so. In the South, most blacks had been disfranchised from 1890–1911 by constitutional changes and discriminatory legislation after southern Democrats regained power in the state legislatures. Unable to vote, blacks were disqualified from serving on juries or holding any political office; they had virtually no political power within the official system. In the few cases that came to trial, all-white juries generally never convicted a white man of lynching a black.

A silent protest march by many blacks took place in front of the Capital grounds and White House in 1922 while the bill's constitutionality was being contemplated. A protest sign read, "Congress discusses constitutionality while the smoke of burning bodies darkens the heavens."

The bill was defeated by the white Democratic voting bloc of the South in filibusters in the Senate in December 1922, in 1923 and 1924.

William Borah, a conservative from Idaho, spoke against it. Borah was concerned about issues of state sovereignty and believed that the bill was not constitutional. He was especially concerned about the clause that provided for federal authorities to punish state officials "remiss in the suppression of lynchings." A prolonged filibuster by Southern white Democrats prevented consideration of the bill and defeated it. After the Democrats had held up voting on all the national business in the Senate for a week in December 1922 by their filibuster, the Republicans realized they could not overcome the tactic and finally conceded defeat on Dyer's bill.

Senator Lee S. Overman of North Carolina told the New York Times that the "good negroes of the South did not want the legislation for 'they do not need it'."

Following the defeat of his first bill in the Senate in 1922, Dyer tried unsuccessfully two more times to get it passed by the Senate. Some of the bill's opponents claimed that the threat of lynching protected white women from sexual advances from black men. The studies by the journalist Ida B. Wells in the late 1890s had shown that black lynch victims were accused or rape or attempted rape only one third of the time. Rather, the murders of blacks were an extreme form of white extrajudicial punishment and community control, often targeting blacks who were economic competitors with whites, who were trying to advance in society, who were in debt to landowners (settlement season for sharecroppers was a time of high rates of lynchings in rural areas), or those who failed to "stay in their place".

In 1919, according to the Pittsburg Gazette Times, many Southerners viewed the practice of lynching as a sporting event.

In 1923 to gain national support for his anti-lynching bill, which was to be heard again that year in the Senate, Dyer toured the western United States to generate public support. His motto for his anti-lynching campaign was "We have just begun to fight." (This was the statement made famous by John Paul Jones.) Dyer attracted mixed black and white audiences in Denver, Portland, Los Angeles, Omaha, and Chicago. He thanked the National Association for the Advancement of Colored People (NAACP) for supporting his bill and praised their continuing to publicize the terrible human toll of lynching in the United States. In Chicago, 4000 people attended his anti-lynching rally. Dyer's campaign received positive coverage by the white mainstream press, which helped strengthen an anti-lynching movement in the West.

The national attention received by Dyer's anti-lynching bill and speaking campaign may have helped reduce lynchings in the South. Lynchings per year dropped in four years, from 60 in 1918 to 57 in 1922. More significantly, the Great Migration was underway, and black workers by the tens of thousands were leaving the South for Northern and Midwestern industrial cities, for jobs, education, and a chance to escape Jim Crow laws and violence.

By 1934, when the Costigan-Wagner anti-lynching bill was introduced, lynchings had dropped to 15 per year. In 1935 and 1938, Senator Borah repeated his constitutional arguments against the bill; he added that he believed such legislation was no longer needed, because the rate of lynchings had fallen so dramatically.

By 1940, 1.5 million blacks had left the South in the Great Migration. Another five million left from 1940–1970.

The political power of the white Democrats in the South came from their having disfranchised most blacks from 1890–1910. The South was essentially a one-party, Democratic region in which only whites voted and held office, well into the 1960s, but Congressional representation was based on the total population. The situation of disfranchisement did not change markedly until passage in the 1960s of federal civil rights legislation that protected and enforced the constitutional rights of voting and citizenship for African Americans and other minorities.

From 1882–1968, "...nearly 200 anti-lynching bills were introduced in Congress, and three passed the House. Seven presidents between 1890 and 1952 petitioned Congress to pass a federal law." None was approved by the Senate because of the powerful opposition of the Southern Democratic voting bloc. In June 2005, through passing a bipartisan resolution sponsored by senators Mary Landrieu of Louisiana and George Allen of Virginia, the US Senate officially apologized for not having passed an anti-lynching law "when it was most needed."