By the age of twenty-two, he was already among the strongest chess players in the world. During the 1920s, he won most of the tournaments in which he played. In 1927, he became the fourth World Chess Champion by defeating Capablanca, widely considered invincible, in what would stand as the longest chess championship match held until 1985.

In the early 1930s, Alekhine dominated tournament play and won two top-class tournaments by large margins. He also played first board for France in five Chess Olympiads, winning individual prizes in each (four medals and a brilliancy prize). His tournament record became more erratic from the mid-1930s onwards, and alcoholism is often blamed for his decline. Alekhine offered Capablanca a rematch on the same demanding terms that Capablanca had set for him, and negotiations dragged on for years without making much progress. Meanwhile, Alekhine defended his title with ease against Bogoljubov in 1929 and 1934. He was defeated by Euwe in 1935, but regained his crown in the 1937 rematch. His tournament record, however, remained uneven, and rising young stars like Keres, Fine, and Botvinnik threatened his title. Negotiations for a title match with Keres or Botvinnik were halted by the outbreak of World War II in Europe in 1939.

Alekhine stayed in Nazi-occupied Europe during the war, where he played in tournaments which were organised by the Nazis. Anti-Semitic articles appeared under his name, although he later claimed they were forged by the Nazis. Alekhine had good relationships with several Jewish chess players, and his fourth wife was Jewish. After the war, Alekhine was ostracized by players and tournament organizers because of the anti-Semitic articles. Negotiations with Mikhail Botvinnik for a world title match were proceeding in 1946 when Alekhine died in Portugal, in unclear circumstances.