De los Santos was called up to Houston in August 1974 after a season dominating hitters in the Double-A Southern League. Pitching in 42 games for the Columbus Astros, he struck out 73 batters in 76 innings and allowed only 11 earned runs. He was 7–4 with an ERA of 1.30.\n', '

On August 21, 1974 de los Santos made his major league debut in relief against the New York Mets at the Astrodome. He retired the first batter he faced, right fielder Rusty Staub, then struck out first baseman John Milner to end the 6th inning. In 2.2 innings that night he gave up two hits, three walks, and two unearned runs, and the Astros lost, 10–2. They had made five errors during the game.\n', '

De los Santos won his first and only big league game one week later at Shea Stadium. He retired Mets shortstop Bud Harrelson, the last hitter in the bottom of the 9th, and then teammate Cliff Johnson hit a home run in the top of the 10th to win the game, 3–2.\n', '

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