Russian President Vladimir Putin lauded Zakharchenko as "a true people's leader" and promised residents of Donetsk that "Russia always will be with you".
Putin issued a statement Friday praising Zakharchenko as a "courageous and decisive person, a patriot". Putin expressed his condolences to Zakharchenko's family.
He said at the time his ambition was to build "a new state".
Among those killed was Arseny Pavlov, who went by the nom de guerre "Motorola" and was blown up in the lift of his apartment building in Donetsk in October 2016.
Ukrainians say he filled a mostly figurehead position for the Russian security service agencies that manage and finance the breakaway regions of Donetsk and Luhansk, and they attributed his death to infighting in the rebel ranks or a Russian targeted killing. Kiev denied any involvement in the blast and blamed separatist infighting.
Russian-backed rebels threw off Ukrainian central rule in an armed uprising after pro-Western leaders opposed by Moscow came to power in the Ukrainian capital, Kyiv, in 2014.
Russian foreign ministry spokeswoman Maria Zakharova said "there is every reason to believe that the Kiev regime is behind the murder".
Russia's Foreign Ministry blamed the assassination on Kiev, saying that the Ukrainian government "decided to start a massacre after failing to fulfill their promises on peace".
Mr Zakharchenko, 42, had been leader since 2014, the year that parts of eastern Ukraine dominated by Russian Federation seceded, leading to a bloody struggle with government troops that continues sporadically today.
Rebel authorities in east Ukraine have detained several suspects and declared three days of mourning after the assassination of top separatist leader Alexander Zakharchenko. A vote held by separatists confirmed him in office.
He took the reins as the leader of the Donetsk Republic in November 2014 from a number of of Russians, in a bid to show that Ukraine's separatist movement wasn't a Russian-led operation.
Interfax news agency reported a source saying that a...
In the past, at least five other leading separatist commanders have been killed in unexplained circumstances not connected to front-line combat.
Another prominent casualty was Alexander Bednov, nicknamed "Batman", a senior commander in the Luhansk People's Republic, another eastern Ukrainian breakaway region that neighbors Donetsk.
Zakharchenko's killing was the latest in a series of violent deaths of separatist officials and commanders in eastern Ukraine, where the Moscow-backed separatists have been fighting Ukrainian forces since 2014 in a war that has killed more than 10,300.