Johan Santana with 265 strikeouts in 2004.
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Matt Kilroy holds the record for most strikeouts by a pitcher in a single season with 513 in 1886. Nolan Ryan holds the modern day record with 383 in 1973.
Randy Johnson has the most strikeouts by a left handed pitcher. He also has the second most strikeouts all-time and over 300 wins.
In 2012, Justin Verlander of the Detroit Tigers, had the most strikeouts with 239.
As of the 2010 season, the Yankees team record for strikeouts by a pitcher in a season is 248 by Ron Guidry in 1978.
At the time of this question, Mark Buehrle had the most strikeouts, but currently Freddy Garcia does.