Since 1901.
- Nolan Ryan, 1973 (383 strikeouts)
- Sandy Koufax, 1965 (382 strikeouts)
- Randy Johnson, 2001 (372 strikeouts)
- Nolan Ryan, 1974 (367 strikeouts)
- Randy Johnson, 1999 (364 strikeouts)
- Rube Waddell, 1904 (349 strikeouts)
- Bob Feller, 1946 (348 strikeouts)
- Randy Johnson, 2000 (347 strikeouts)
- Nolan Ryan, 1977 (341 strikeouts)
- Randy Johnson, 2002 (334 strikeouts)
- Nolan Ryan, 1972 (329 strikeouts)
- Randy Johnson, 1998 (329 strikeouts)
- Nolan Ryan, 1976 (327 strikeouts)
- Sam McDowell, 1965 (325 strikeouts)
- Curt Schilling, 1997 (319 strikeouts)
- Sandy Koufax, 1966 (317 strikeouts)
- Curt Schilling, 2002 (316 strikeouts)
- Walter Johnson, 1910 (313 strikeouts)
- J.R. Richard, 1979 (313 strikeouts)
- Pedro Martinez, 1999 (313 strikeouts)
- Steve Carlton, 1972 (310 strikeouts)
- Mickey Lolich, 1971 (308 strikeouts)
- Randy Johnson, 1993 (308 strikeouts)
- Sandy Koufax, 1963 (306 strikeouts)
- Mike Scott, 1986 (306 strikeouts)
- Pedro Martinez, 1997 (305 strikeouts)
- Sam McDowell, 1970 (304 strikeouts)
- Walter Johnson, 1912 (303 strikeouts)
- J.R. Richard, 1978 (303 strikeouts)
- Rube Waddell, 1903 (302 strikeouts)
- Vida Blue, 1971 (301 strikeouts)
- Nolan Ryan, 1989 (301 strikeouts)
- Clayton Kershaw, 2015 (301 strikeouts)
- Chris Sale, 2017 (300 strikeouts and counting)
- Getting hit by a pitch
- Curt Schilling, 1998 (300 strikeouts)