It will close to all traffic at 20:00 GMT and reopen 48 hours later, each weekend until 19 December.
During the works, about 50,000 tonnes of material will be laid on the 2.9km (1.8 mile) runway.
Traditionally, airports close for up to 14 days to carry out such work.
Airport bosses said completing the refurbishment over several weekends rather than all at once was the "best way to avoid major disruption".
The closures were agreed following two years of discussions with retailers and airlines, airport management added.
"Some of our retail partners are refurbishing their shops which they wouldn't be able to do when the airport is open," said Jack Kelly from EMA.
"We've made sure flights can come in ahead of the closure and more flights can go out after it, so we are limiting the amount of disruption."
The runway was last refurbished in 1999 and has a lifespan between 12 to 17 years.
Engineers will also be replacing 1,200 lights around the runway with LEDs.
The runway will be divided up into seven sections, with one chunk being repaired and sealed off each weekend.
East Midlands Airport (EMA) will shut later for the first of seven consecutive weekends to resurface the runway - a first for a UK airport, bosses have said.