A new state-of-the-art building for 1,735 pupils will be built in Rosyth.
The £85 million school on the site of the former Fleet Grounds will replace the ageing Hillend Road building, which is in need of a significant upgrade.
The decision followed a widespread public consultation, but there has also been significant opposition from some sections of the community.
Many are unhappy the school will be moved out of Inverkeithing, meaning more children will have to take a bus.
But head of education Shelagh McLean said the educational benefits for children would be significant.
The next stage will be to seek planning permission, and construction is expected to take around two-and-a-half years.
Fife Council’s education spokesperson, Labour councillor Cara Hilton, said she was very pleased with the decision.
And she added: “While there are still some answers needed on what will happen with the current community use facilities at Inverkeithing High School, there was wide agreement between members that a new school building will be a very positive outcome for the children and young people of south west Fife.
“The relocation of Inverkeithing High School will provide us with the opportunity to create a state-of-the-art new facility for learning and teaching.”
Meanwhile, Shelagh McLean said: “The education service is delighted to have approval to progress with this project.
“It’s clear the educational benefits for our children and young people will be significant, as they’ll be able to learn in a purpose-built facility suitable for their education now and in the future.”