Odejayi's brace and an own goal by Miguel Angel Llera ensured Addicks boss Phil Parkinson endured a miserable return to his former club, as the U's extended their own unbeaten run under manager Aidy Boothroyd to five matches.
Deon Burton and Nicky Bailey both went close for Charlton early on, but two Colchester goals in the space of three minutes changed the nature of the game completely.
The U's took the lead in the 28th minute when Llera inexplicably headed Anthony Wordsworth's lofted ball over his own goalkeeper Rob Elliot.
And less than three minutes later, Odejayi latched on to John-Joe O'Toole's long pass to chest down and fire low and decisively past Elliot.
Things got even worse for Charlton 12 minutes after half-time when Odejayi linked up superbly with Kevin Lisbie and beat the Addicks goalkeeper to the ball before slotting in low at the near post.
U's goalkeeper Ben Williams saved superbly from Jonjo Shelvey late on as Charlton slumped to a heavy defeat.
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