Dirksen was born in Pekin, Illinois, a small city near Peoria, He was the son of German immigrants, Antje (Conrady) and Johann Friedrich Dirksen. Everett's parents gave him the middle name "McKinley" for President william McKinley. He had a fraternal twin, Thomas Reed Dirksen (named for Thomas B. Reed), and another brother, Benjamin, named for President Benjamin Harrison. Johann and Antje Dirksen spoke a Low German dialect at home, and taught German to their children, but Johann had lived in the United States long enough to become politically aware; the names of all three boys were a nod to his Republican Party leanings. Johann Dirksen, who worked at the Pekin Wagon Works as a design Painter in addition to farming, had a debilitating stroke when Everett Dirksen was five years old, and he died when Everett Dirksen was nine. He had been Antje's second husband; with her first husband, Beren Ailts (d. 1890), she was the mother of two sons, Everett Dirksen's half brothers Thomas and Henry.

Dirksen grew up on a farm managed by his mother on Pekin's outskirts, in a neighborhood called Bonchefiddle, Low German for "Beantown", because frugal immigrants grew beans for the family dinner table in their front yards instead of decorative flowers. He attended the local schools, graduated from Pekin High School in 1913 as the class salutatorian, and helped support the family by working at a Pekin corn refining factory. A visit to the Minnesota home of one of his half brothers led to Dirksen's attendance at the University of Minnesota. He was a pre-law student from 1914 to 1917, and paid his tuition by working in the Classified advertising department at the Minneapolis Tribune, and as a door-to-door magazine and book salesman, an attorney's assistant, and a clerk in a railroad freight office. While attending college, Dirksen participated in the Student Army Training Corps, and attained the rank of major in the school's corps of cadets. He also gained his first political experience by giving local and on-campus speeches in support of Republican nominee Charles Evans Hughes during the 1916 campaign for President.

Dirksen dropped out of college to enlist in the United States Army. On January 4, 1917 -- his twenty-first birthday -- Dirksen joined the Army. He completed his initial training in field artillery at Camp Custer, Michigan, performed duty with his unit at Camp Jackson, South Carolina, and attained the rank of sergeant. Dirksen went to France in 1918, and attended the artillery school and officer training at Saumur. He was commissioned as a second lieutenant, and assigned to the 328th Field Artillery Regiment, a unit of the 85th Division. Dirksen was trained as an aerial observer, and conducted target acquisition and assessment of field artillery bombardments in the Saint-Mihiel sector as a member of the 328th Field Artillery's 13th and 19th Balloon Companies. He later performed the same duty for the 69th Balloon Company, a unit of the IV Corps. He subsequently served in the Intelligence staff section (G-2) of the IV Corps headquarters. Dirksen performed post-war occupation duty with IV Corps in Germany until mid-1919. Offered the opportunity to remain with the Army of Occupation because of his fluency in German, Dirksen declined, received his discharge, and returned to Pekin.

His political career began in 1926, when he was elected to the nonpartisan Pekin City Council. He placed first in field of eight candidates vying for four seats. At the time, the top votegetter also received appointment as the city's commissioner of accounts and Finance, and Dirksen held both posts from 1927 to 1931.

After losing in the 1930 Republican primary, Dirksen won the nomination and the congressional seat in 1932 and was re-elected seven times. His support for many New Deal programs initially marked him as a moderate, pragmatic Republican, though over time he became increasingly conservative and isolationist. During World War II, he lobbied successfully for an expansion of congressional staff resources to eliminate the practice under which House and Senate committees borrowed executive branch personnel to accomplish legislative work. He reversed his isolationist stance to support the war effort, but also secured the passage of an amendment to the Lend Lease Act by introducing it while 65 of the House's Democrats were at a luncheon. It provided that the Senate and the House could, by a simple majority in a concurrent resolution, revoke the war powers granted to the President.

Born in Pekin, Illinois, Dirksen served as an artillery officer during World War I and opened a bakery after the war. After serving on the Pekin City Council, he won election to the House of Representatives in 1932. In the House, he was considered a moderate and supported much of the New Deal; he became more conservative and isolationist over time, but reversed himself to support US involvement in World War II. He won election to the Senate in 1950, unseating Senate Majority Leader Scott W. Lucas. In the Senate, he favored conservative economic policies and supported the internationalism of President Dwight D. Eisenhower. Dirksen succeeded william F. Knowland as Senate Minority Leader after the latter declined to seek re-election in 1958.

Dirksen studied law privately in Washington, D.C., after he was elected. He was admitted to the District of Columbia Bar in 1936 and the bar of Illinois in 1937.

In December 1943, Dirksen announced that he would be a candidate for the Republican presidential nomination in 1944. He stated that a coalition of midwestern Republican representatives had urged him to run and that his campaign was serious. However, press pundits had assumed that the candidacy was a vehicle to siphon support away from the campaign of Wendell Willkie, whose reputation as a maverick and staunch internationalist had earned him the hatred of many Republican Party regulars, especially in the Midwest. Dirksen's presidential campaign was apparently still alive on the eve of the 1944 convention, as Time speculated that he was running for vice-president. Dirksen received no votes for either office from delegates at the convention.

Dirksen continued to be re-elected. In 1947, he began to experience trouble in his right eye, which was diagnosed as chorioretinitis. Despite a number of Physicians (including one from Johns Hopkins University) recommending for the eye to be removed, Dirksen chose treatment and rest; he recovered most of the sight in that eye. In 1948, he declined to run for re-election because of his ailment. He returned to politics two years later and was elected to the U.S. Senate.

Dirksen was elected as senator in 1950, when he unseated Senate Majority Leader Scott W. Lucas. In the campaign, the support of Wisconsin Senator Joseph McCarthy helped Dirksen gain a narrow victory. As an ally of McCarthy, Dirksen tried but failed to get him to apologize for his misdeeds to stave off his censure in 1954, which Dirksen voted against. Dirksen's canny political skill, rumpled appearance, and convincing if sometimes flowery overblown oratory (which made his critics call him "the Wizard of Ooze") earned him a prominent national reputation.

In 1952, Dirksen supported the presidential candidacy of fellow Senator Robert A. Taft of Ohio, the longtime leader of the Republican party's conservative wing. At the national party convention, Dirksen gave a speech attacking New York Governor Thomas E. Dewey, a liberal Republican and the leading supporter of General Dwight Eisenhower, the commander of the Allied forces in Europe in World War II and Taft's opponent for the Republican presidential nomination. During his speech, Dirksen pointed at Dewey on the convention floor and shouted, "Don't take us down the path to defeat again," a reference to Dewey's presidential defeats in 1944 and 1948. His speech was met by cheers from conservative delegates and loud boos from pro-Eisenhower delegates. After Eisenhower won the nomination, Dirksen then supported him.

Dirksen was a Freemason and was a member of Pekin Lodge #29 in Pekin. In 1954, he was Grand Orator of the Grand Lodge of Illinois. He was honored with the 33rd degree in 1954.

In 1959, he was elected Senate Minority Leader, defeating Kentucky's more liberal senator, John Sherman Cooper, 20-14. Dirksen successfully united the various factions of the Republican Party by granting younger Republicans more representation in the Senate leadership and better committee appointments. He held the position of Senate Minority Leader until his death.

Along with Charles Halleck and later, Gerald Ford, his contemporaries as House Minority Leaders, Dirksen was the official voice of the Republican Party during most of the 1960s. He discussed politics on television news programs. On several occasions, political Cartoonist Herblock depicted Dirksen and Halleck as vaudeville song-and-dance men, wearing identical elaborate costumes and performing an act called "The Ev and Charlie Show."

In 1964, as Southern Democratic Senators staged a filibuster, which ran 54 days to block passage of the Civil Rights Act of 1964, Dirksen, Thomas Kuchel (R-CA), Hubert Humphrey (D-MN), and Mike Mansfield (D-MT) introduced a substitute bill that they hoped would attract enough swing votes to end the filibuster. It was weaker than the House version, on the government's power to regulate the conduct of private Business, but it was not so weak it would cause the House to reconsider the legislation. Also, the Department of Justice said the Mansfield-Dirksen Amendment would not prevent effective enforcement. However, Senator Richard Russell, Jr. (D-GA) refused to allow a vote on the amendment. Finally, Senator Thruston Morton (R-KY) proposed an amendment that guaranteed jury trials in all Criminal contempt cases except voting rights. It was approved on June 9, and Humphrey made a deal with three Republicans to substitute it for the Mansfield-Dirksen Amendment in exchange for their supporting cloture on the filibuster. Thus, after 57 days of filibuster, the substitute bill passed in the Senate, and the House–Senate conference committee agreed to adopt the Senate version of the bill.

On March 22, 1966, Dirksen introduced a constitutional amendment to permit public school administrators providing for organized prayer by students; the introduction was in response to Engel v. Vitale, which struck down the practice. Considered by opponents to violate the principle of separation of church and state, the amendment was defeated in the Senate and gained only 49 affirmative votes, far short of the 67 votes a constitutional amendment needs for passage. Dirksen was a firm opponent of the doctrine of one man, one vote on the grounds that large cities (such as Chicago in Dirksen's home state of Illinois) could render rural residents of a state powerless in their state governments; after the Warren Court imposed one-man-one-vote on all state legislative houses in Reynolds v. Sims, he led an effort to convene an Article V convention for an amendment to the Constitution that would allow for legislative districts of unequal population. Dirksen died before enough states passed resolutions for the convention, by which point the court-ordered re-engineered legislatures began repealing their predecessors' resolutions.

In August 1969, chest x-rays disclosed an asymptomatic peripherally located mass in the upper lobe of the right lung. Dirksen entered Walter Reed Army Hospital for surgery, which was undertaken on September 2. A right upper lobectomy removed what proved to be lung cancer (adenocarcinoma). Mr. Dirksen initially did well, but progressive complications developed into bronchopneumonia. He suffered a cardiopulmonary arrest and died on September 7, 1969, at age 73.

Dirksen was also known for his fondness for the Common marigold. When political discussions became tense, he would lighten the atmosphere by taking up his perennial campaign to have the marigold named the national flower, but it never succeeded. In 1972 his hometown of Pekin started holding an annual Marigold Festival in his memory. It now identifies itself as the "Marigold Capital of the World."

Dirksen's widow, Louella, died of cancer on July 16, 1979. Their daughter Joy, the first wife of Senator Howard Baker of Tennessee, died of cancer on April 24, 1993.

He was a member of the Reformed Church in America, founded in the 18th century by Dutch immigrants.