In a statement, Tehran Friday Prayers Headquarters announced that the sermon will be held at Tehran's Mosalla mosque, adding, "the Iranian nation will once again demonstrate their unity and magnificence", said a report in Iran's Mehr news agency.
But the report did not link the prayer session to the current situation.
The last time Khamenei led Friday prayers in Tehran was in 2012 on the 33rd anniversary of the country's Islamic Revolution.
Leading Friday prayers in the capital is a symbolically significant act usually reserved for times when Iran's highest authority wishes to deliver an important message, the BBC reported citing Mehdi Khalaji of The Washington Institute for Near East Policy, as saying.
Historically, Iranian leaders have left this task to loyal clerics with strong oratorical skills, he added.
Social media footage from several funerals held for victims on Thursday showed mourners chanting slogans against the authorities.
Protests erupted across Iran after the Islamic Revolutionary Guards Corps (IRGC) on January 12 admitted that the plane had been mistaken for a "cruise missile" during heightened tensions with the US.
The Ukraine International Airlines Boeing 737-800 was travelling to Kiev from Tehran on January 8 when it crashed shortly after take-off. All 176 passengers on board, including dozens of Iran and Canad, were killed.
Hours before the plane was shot down, Iranian missiles had also targeted two airbases in Iraq that housed US forces.
That rocket attack was in retaliation to the January 3 killing of Iranian Major General Qasem Soleimani, who was the chief of the IRGC's elite Quds Force, by an American drone near the Baghdad airport.
( With inputs from IANS )