Pettitte struck out the Minnesota Twins' Justin Morneau in the fifth inning on Monday night to give him 1,958 for his career. Ford has held the mark since he retired in 1967.
Pettitte entered the game needing two strikeouts to break the record. He fanned Clete Thomas in the second inning to tie Ford, then got Morneau swinging in the fifth.
Pettitte gave up four runs over five innings as the Yankees, backed by Robinson Cano's two home runs, snapped a five-game skid with a 10-4 victory over the Twins.
"I feel very fortunate to be around for as long as I have," Pettitte said. "To be able to be mentioned with Whitey's name is obviously always an honor."
The three-time All-Star broke into the big leagues with the Yankees in 1995 and has spent all but three of his 18 seasons in pinstripes.
Information from The Associated Press was used in this report.