Birmingham's King Edward VI High School for Girls scooped a double after being named the best independent for both GCSEs and A level results nationally.
Head teacher Sarah Evans said it was a first for the school and a major boost to the region.
"It sends a strong message about the Midlands having the best independent school in the country," she said.
"People moving to the Midlands will know they have the best here."
Although it beat some of the country's most exclusive public schools - including Eton and Harrow - the school fell behind some schools in the maintained sector.
For GCSEs it came ninth nationally, with the nonselecting Midland comprehensive Thomas Telford at the top when schools in the maintained sector are included.
It was also behind the grammar Wolverhampton Girls' High School for GCSEs.
For A levels, the school came third nationally when all schools are considered. It was behind two grammar schools in the south.
Ms Evans added: "It is not just about going on and on getting good exam results. We want our pupils to be excited by learning and have the opportunity to do lots of extra-curricular activities.
"We are always trying to take them beyond the fairly pedestrian issue of examinations."