"In 1974, according to beat writers in attendance, Ryan threw 259 pitches in a 12-inning win over Kansas City."
"On May 1, 1920, Brooklyn and Boston played a 1-1 tie that lasted 26 innings. Incredibly, pitchers Leon Cadore and Joe Oeschger each went the distance. Historians estimate that Cadore threw 345 pitches, Oeschger 319."
"...1963 matchup between the Giants' Juan Marichal and the Braves' Warren Spahn, each going the distance in a 16-inning game that ended on Willie Mays' homer. Marichal threw 227 pitches that night, and there was a point when his catcher, Ed Bailey, told him, "Don't let them take you out. Win or lose, this is great.""
April 27, 1993: Pirates knuckler Tim Wakefield tossed 172 pitches over 10+ innings in a 6-2 victory against the Atlanta Braves at Atlanta-Fulton County stadium. (Wakefield scored one of four Pirate runs in the 11th inning but was lifted after walking the first two batters in the bottom of the 11th.).
In the playoffs, the record is held by Luis Tiant, who threw 163 pitches in Game 4 of the 1975 World Series, a complete-game win for the Red Sox.
Tom Cheney of the Washington Senators threw 228 pitches in a 16 inning complete game victory over the Baltimore Orioles in 1962. In this game Cheney struckout 21 batters which, as of 2010, is the MLB record for most batters struckout by a pitcher in a game.
Without checking, Cy Young. He threw waaaaay more innings than anyone else. Pitch count data is spotty at best prior to the 1990s, but according the baseball-reference.com the most pitches thrown: in a single game is: 5/17/61, 207 pitches by Stan Williams in 11 innings in a single season is: 4052 by Randy Johnson in 2001. Obviously nowhere near the record, but it's the best we've got.
In 1944, Charley "Red" Barrett of the Boston Braves threw only FIFTY-EIGHT pitches during a nine inning complete game. Barrett's Braves shutout the Reds 2 - 0 and the game set major league records for least number of pitches known to have been thrown by a single pitcher in a complete game and shortest game played at night.
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