Frank E. Fitzsimmons, 73, general president of the International Brotherhood of Teamsters, the largest labor union in the United States, died of lung cancer yesterday at the Scripps Clinic in La Jolla, Calif.

His death occurred after three weeks of "chemotherapy-related treatment" at the California clinic, according to a clinic spokesman.

Mr. Fitzsimmons' death is expected to trigger a major battle for leadership of the 2.3 million-member union, which is famous for its ability to organize American workers and infamous for its numerous brushes with the law.

Mr. Fitzsimmons had run the union since 1967, when he was handpicked by former Teamsters president James R. (Jimmy) Hoffa to be general executive vice president.

It was a publicly known caretaker arrangement, designed and executed by Hoffa, who then was facing a 13-year federal prison term on pension fund fraud and jury-tampering convictions.

Hoffa served four years of the sentence, during which time he retained the title of general president of the union. The remainder of his term was commuted by then-president Richard M. Nixon on Dec. 23, 1971. Nixon's action carried with it the stipulation that Hoffa stay out of union politics for 10 years.

The legal ban gave Mr. Fitzsimmons the chance to take over the union in his own right, an achievement he realized in Miami Beach, Fla., on July 8, 1971, when he was elected general president over token but bitter opposition. His victory ended nearly four decades of working in Hoffa's shadow. It also ended the increasingly strained friendship between the two men.

Hoffa had not given up his dream for a comeback as Teamsters czar. He publicly announced his timetable for regaining the union's leadership in 1976 when the next Teamsters international convention was scheduled to take place.

Hoffa's dream remained a dream. On July 30, 1975, he disappeared under mysterious circumstances. Law enforcement officials suspected foul play. His whereabouts remain unknown.

As president of the Teamsters, Mr. Fitzsimmons radically changed the structure under which the union operated. Under Hoffa, the Teamsters union was highly centralized. International vice presidents reported to him. Regional and local union decisions were largely subject to his veto or approval. Hoffa, in effect, was the Teamsters.

Mr. Fitzsimmons yielded to growing demands among the union's rank-and-file for increased automomy. He gave his international vice presidents policy making roles and allowed Teamsters locals pretty much to run their own affairs.

For that and other achievements -- especially for his aggressiveness in organizing the unorganized -- Mr. Fitzsimmons was praised yesterday by AFL-CIO President Lane Kirkland and the federation's secretary-treasurer, Thomas Donahue, for building a union that represents "the best interest of its members."

"We are saddened by the death of Frank Fitzsimmons," the AFL-CIO leaders said in a joint statement."He cooperated with many of our affiliates on issues of mutual concern to America's working men and women."

President Reagan, whom Mr. Fitzsimmons supported in last November's election, issued a statement from the White House, praising Mr. Fitzsimmons as "an important and powerful voice in the American labor movement. His death is a sad moment, not only for the millions of Teamster union members he so diligently represented, but for our nation as well."

The president called the labor leader "affable and humorous" and said that "from his earliest days as a labor organizer in the 1930s, [he was] a hard bargainer who won the respect of both business and political leaders throughout the nation."

Kirkland had hoped that that cooperation between the Teamsters and the AFL-CIO would lead to the Teamsters reaffiliation with the federation, from which the union had been expelled in 1957 for failure to change alleged corrupt practices.

Mr Fitzsimmons reportedly was in favor of rejoining the federation. But several AFL-CIO sources expressed doubts yesterday that this would come about soon, especially because of political battles that are expected to follow among Mr. Fitzsimmons' successors.

Despite his closeness to Reagan and the improved relations he had helped bring about with the AFL-CIO, Mr. Fitzsimmons was a codefendent in a multibillion-dollar civil suit brought by the Department of Labor in connection with alleged misuse of assets in the Teamsters Central States Pension Fund. There was no allegation that Mr. Fitzsimmons had enriched himself by reason of his position in the union.

Mr. Fitzsimmons was born in Jeanette, Pa. At the age of 16, following the death of his father, he dropped out of high school and went to work in Detroit. In what later would be deemed a propitious move, he joined Teamsters Local 299 in 1934.

"Two-ninety-nine," as he is called in Detroit, was Hoffa's local and the gateway to power in the Teamsters. Hoffa was impressed with Fitzsimmons' activism and loyalty, and in 1937, named him Local 299's business agent.

Hoffa rose, and "Fitz," as his friends called him, followed. The relationship lasted until their final break in 1971.

At his death, Mr. Fitzsimmons, for whom the Teamsters union maintained homes in Kenwood, Md., and La Costa, Calif., commanded the highest annual salary paid to a union leader, $174,794, including wages and fringe benefits. And because of his support of Reagan, he also commanded something that other labor leaders, including Kirkland, lacked -- access to political power.

Survivors include his wife, Mary Patricia Fitzsimmons, and four children, two of whom are by an earlier marriage.