Redland High School said its buildings "no longer meet the demands of a 21st century education" and it would be merging with Red Maids' School, which was founded in 1634.
The new school, Redmaids' High School, will operate from the current Red Maids' site in Westbury-on-Trym.
Red Maids' head, Isabel Tobias, will also head the newly merged school.
Dr Tim Chambers, chair of governors at Redland High School, said education expectations had changed and their "beautiful but inflexible 18th century listed buildings no longer meet the demands of a 21st century education".
"A considerably larger number of pupils is needed in the modern educational world to create the strong balance sheet to be sustainable and to invest in the educational provision our girls deserve," he added.
"We can never achieve that alone on our current site."
Two of Bristol's private schools are to merge.