The actress, who was cast in the BBC drama in late 2009, has already filmed her final scenes as school head teacher Karen, The Sun reports.
Sources told the newspaper that Burton had struggled spending time away from her family home in London while filming the programme in Rochdale, Greater Manchester.
Meanwhile, Burton's agent confirmed her departure, explaining that she had decided not to renew her contract.
A show insider added: "It's a shame as viewers really liked her character."
Karen was on screen throughout series six of Waterloo Road and also features in the first block of series seven episodes, which begin next Wednesday on BBC One.
Waterloo Road's seventh series sees Robson Green join the cast as the school's new site manager Rob Scotcher, who has been tipped as a possible new love interest for Karen.
A BBC spokesperson told DS this morning: "Amanda has made an amazing contribution to Waterloo Road playing Karen Fisher. We hope the viewers will enjoy seeing how her relationship with Rob Scotcher plays out over the next 10 weeks."
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