The 47-year-old joined the Channel 4 quiz show alongside Richard Whiteley when it began in 1982.
She has since co-hosted with Des Lynam and current frontman Des O'Connor.
The news follows O'Connor's announcement that he will step down from the programme in November. Comedian Rory Bremner is reported to be the favourite to replace him.
Vorderman is rumoured to have walked out after failing to agree a new contract amid attempts by the show's producers to cut costs.
She is said to be "extremely sad" over the decision.