As a representative-elect in December 1922, Celler forcefully criticized the Second Ku Klux Klan as "a national menace," a "canker and disease that is harassing our body politic," and "worse than Bolshevism.

This national origin system was structured to preserve the ethnic and religious identity of the United States by reducing immigration from Eastern and Southern Europe, thereby excluding many Jews, Catholics, among others.

Celler had found his cause and for the next four decades he vigorously spoke out in favor of eliminating the national origin quotas as a basis for immigration restriction.

[3] In the 1940s, Celler opposed both the isolationists and the Franklin D. Roosevelt administration by forcefully advocating that the United States relax immigration laws on an emergency basis to rescue those fleeing the Holocaust.

Celler was also a Zionist who supported the recognition of Israel and requested the lifting of the American embargo imposed on both sides during the 1948 Palestine war.

In 1951, Celler conducted hearings in the United States House Judiciary Committee to examine the anti-trust exemption granted to Major League Baseball (MLB).

[8] Celler's final report suggested that the Congress should take no action, allowing for the matter to be settled in the federal judiciary of the United States.

In 1953, the Supreme Court of the United States upheld MLB's anti-trust exemption and the reserve clause in Toolson v. New York Yankees, Inc..[7] In the early 1950s, the Republican Senator Joseph McCarthy attacked Celler's patriotism.

At the 1952 Democratic National Convention, Celler gave a speech in which he responded to Sen. McCarthy, saying: "Deliberately and calculatedly, McCarthyism has set before itself the task of undermining the faith of the people in their Government.

He worked closely with Rep. William Moore McCulloch (R-OH), the Ranking Member, to craft sufficient bipartisan support in the House to overwhelm Southern Democrat opposition in the Senate.

During the Watergate scandal of 1973–1974, he was a frequent guest on television and radio programs, discussing the hearings and the position of Chairman of the Judiciary Committee, which he held for a record number of years.