The road from Rowsley to Chatsworth - the B6012 - will be closed over three days.
The closure will be in place from 7am on Sunday until around midnight on Tuesday to allow Severn Trent to repair a collapsed pipe.
A fully signed diversion will be in place.
The diversion is around 10 miles through Bakewell.
A Severn Trent spokesperson said: "W would like to apologise to anyone affected by the road closure."