David Worrall almost put Southend ahead, nodding against the post before keeper Tommy Lee saved his rebound.
Chesterfield's Ollie Banks and the hosts' Tyrone Barnett both threatened, while Southend had a penalty turned down when Sam Hird felled David Mooney.
With time running out, Banks teed up Novak to win it with a neat finish.
Lee Novak scored a last-minute winner as Chesterfield beat League One play-off chasers Southend to move six points clear of the relegation zone.