After announcing a state of emergency, authorities closed all checkpoints leading into the war-torn city and postponed the start of the school year.
According to early reports, Mr Zakharchenko was killed by an explosive device hidden in the cafe on Pushkin Boulevard in central Donetsk.
Tax Minister Alexander Timofeyev was also treated in hospital for serious injuries. Mr Timofeyev is considered one of the separatist leader’s closest colleagues; Mr Zakharchenko was godfather to his children.
Mr Zakharchenko, 42, was anointed leader of the self-proclaimed Donetsk People’s Republic by Russian handlers in November 2014. He is the latest in a series of separatist leaders to have been killed during the conflict in eastern Ukraine, where more than 10,000 people are believed to have died since fighting broke out between Kremlin-backed separatists and pro-Ukrainian government forces that year.
Mr Zakharchenko was known as a volatile leader, happiest on the frontline and restless away from war. His arm was injured in 2014 and he spent much of 2015 hobbling on crutches after being injured in the battles around Debaltseve in January and February that year.
Mr Zakharchenko’s hotheaded nature meant that he would often appear out of sync with curators in Moscow. Unlike fellow rebel commanders, however, he was known for eventually coming round to more moderate positions.
The former coal-mine electrician also had a simple manner that made him a popular, if unorthodox, figurehead among certain parts of the population.
Separatist authorities have been quick to assert subversive groups loyal to Kiev were responsible for the assassination. They already claim to have arrested “Ukrainian agents”.
Russia has also said it believed Kiev was responsible for the death. Vladimir Putin called him “courageous and decisive”. A spokeswoman for Russia’s foreign ministry, Maria Zakharova, said Mr Zakharchenko’s death showed Kiev had decided to engage in a “bloody fight” and had turned away from its promises of seeking peace.
But this is not the only – or even the most likely – explanation of the assassination. At first inspection, internal disputes, battles for cash, and the targeted work of Russian security services seem more obvious lines of inquiry.
Rifts between the separatist factions are the one permanent feature of a conflict entering its fifth year. Often backed by competing groups in Moscow, the rivalry has regularly spilt over into violence.
Several commanders have met their end in highly suspicious circumstances – with few of their colleagues believing the same official line of Ukrainian diversionary activity.
Mr Zakharchenko certainly had no shortage of enemies. Wherever there was money to be made, he was there. He was often in obvious conflict with the other strongman commander in Donetsk, Alexander Khodarkovsky.
In recent months, it was reported that Moscow was preparing to replace him with someone more reliable and presentable to the outside world. The name most often mentioned was the milder-mannered Denis Pushilin, a former pyramid-scheme marketeer and chairman of the separatist’s self-proclaimed parliament.
Mr Pushilin is the separatists’ representative at the three-way contact group at the Minsk negotiations aimed at ending the conflict. He is known to be more amenable to the Russian positions of returning the separatist republics as autonomous constituent parts of Ukraine.
Ukrainian security services denied any involvement in the incident. Speaking on Ukrainian television, their representative Igor Guskov said Mr Zakharchenko had become a difficult man for his Russian handlers.
“We do not rule out an attempt from Russian security services to do away with an odious figure … who got in the way,” Mr Guskov said.
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