He was born on 26 June 1976 in Donetsk in the family of a miner, Vladimir Zakharchenko. His father is Ukrainian by nationality, his mother Tamara Zakharchenko is Russian. He graduated from secondary school No. 4 in Donetsk. According to his biographical data from Russian sources, he graduated from the Donetsk Technical School of Industrial Automation (with honours), worked as a miner, an electromechanic and was involved in business.

During the pro-Russian protests in eastern Ukraine, he led the Donetsk branch of the Kharkiv-based Oplot fight club. On 16 April 2014, he led a group of 7 militants who occupied the building of the Donetsk City Administration. He was in charge of 'Oplot' until 7 July 2014.

In May 2014, he was appointed "military commandant" of Donetsk captured by militants. Later, in July of the same year, he was appointed "Deputy Minister of Internal Affairs of the DPR" with the rank of police major. As a member of 'Oplot', he took part in attacks on the Donetsk airport controlled by Ukrainian troops. In June 2014, he was wounded in those battles.

On 7 August 2014, he replaced Alexander Boroday as the head of the Council of Ministers of the 'DPR'.

On 11 August 2014, Oleksandr Zakharchenko made a statement that "DPR units are ready for offensive actions" and that a "broad, normal offensive" would begin in the coming days. Russian news outlets disseminated information that the 'militia and self-defence' had acquired over 200 armoured vehicles to be used in the announced 'counter-offensive'. On the night of 12-13 September, battalion tactical groups of the 17th motorised rifle and 18th motorised rifle brigades of the Russian Armed Forces crossed the border near Marynivka and Stepanivka.

On 24 August, in the morning, Alexander Zakharchenko announced a "large-scale offensive in all directions". The same morning, a column of 100 Russian military vehicles moved from the state border, surrounding Ukrainian forces near Ilovaisk.

In January 2015, militants resumed attacks on the Ukrainian military-controlled town of Debaltseve. In order to stop the brutal fighting, the leaders of the Normandy Four met in Minsk on 11 February, which resulted in the signing of the Package of Measures for the Implementation of the Minsk Protocol by the participants in the Minsk process. The document was also signed by DPR leader Zakharchenko and LPR leader Plotnitsky without specifying their positions.

Despite the fact that, according to the agreement, a complete ceasefire was to be established on the contact line from midnight on 15 February, the fighting for Debaltseve continued until the Ukrainian army was forced to leave the city and its surroundings under pressure from Russian troops and militants; Zakharchenko stated that the settlement of the cessation of fighting in the Debaltseve area was not a subject of the signed agreements. Zakharchenko himself was wounded during the fighting in Debaltseve.

On 3 November, after the illegitimate and rigged elections in the DPR, the unrecognised CEC of the republic announced that Zakharchenko had won: 765,000 people voted for him, which was about 75% of the electorate. On 4 November, an inauguration took place at the Donetsk Music and Drama Theatre, during which, according to eyewitnesses, Zakharchenko took the oath of office and received a certificate of the head of the DPR from the head of the DPR CEC, Roman Lyagin. He received two St George's Crosses of the DPR.

During the war in Donbas, there were many cases of enforced disappearances in the Russian-occupied territory. On 22 January 2015, Zakharchenko said that his troops detained up to five "Ukrainian subversives" aged 18 to 35 every day. On 2 June 2017, journalist Stanislav Aseyev was abducted.

On 16 July 2017, the militants reported that the blogger was detained on charges of 'espionage'. Amnesty International demanded that Zakharchenko release the journalist.

He died on 31 August 2018 as a result of an explosion in the Separ restaurant on Pushkin Boulevard in Donetsk. During the explosion, he sustained a non-life-threatening brain injury. The Minister of Revenue and Duties of the DPR Alexander Timofeev ("Tashkent") and two other people were also injured. Initially, it was reported that Tashkent had been killed, but the news was not confirmed. Another victim was Zakharchenko's bodyguard. The incident took place on the day of mourning for the death of Iosif Kobzon. The cafe belonged to the head of Zakharchenko's security. Local collaborators blame Zakharchenko's death on two detained 'Ukrainian saboteurs' and Zakharchenko's personal bodyguard, who fled the scene. According to inaccurate information, the explosive device was in a lantern that was near the table, and the main wounds were received in the head, he died in hospital.