In 2010, he had his candidacy nominated for the Party of Regions in the 2010 Ukrainian local elections as mayor of Kharkiv.

[15] Kernes was noted for holding a strongly 'pro-Russian' stance and for being a supporter of then-President of Ukraine Viktor Yanukovych.

[17] Following the Revolution of Dignity, after he and the governor of Kharkiv Oblast, Mykhailo Dobkin, had briefly found refuge in Russia,[18] Kernes was accused of alleged connections to death threats, kidnapping and torturing of participants of Euromaidan in Kharkiv and was subsequently placed under night-time house arrest.

[23] In March 2014 he stated that he had been a "prisoner of Yanukovych's system" and that he expected "good things to come" from the new Yatsenyuk Government.

[27] While recovering in Israel, Kernes stated on 11 June 2014 his willingness to cooperate with newly inaugurated Ukrainian President Petro Poroshenko.

After his re-election, Kernes took a position loyal to the new Kyiv government: he made loud statements, but did not take any measures to protect Soviet monuments.

In December 2018, Kernes said that in the 2019 Ukrainian presidential elections he would vote for Petro Poroshenko, as he had made “quite a lot of effort” to finance and develop Kharkiv.

[40] In the July 2019 Ukrainian parliamentary election, Kernes was placed in the top ten of the party list of Opposition Bloc.

[41] However, the nationwide list of this party won just 3.23% of the votes, failing to overcome the 5% election barrier and keeping Kernes from a seat in the Verkhovna Rada.

[44] On 15 September, the Kharkiv City Council officially denied reports that he had gone into a coma after becoming infected with COVID-19 during the COVID-19 pandemic in Ukraine.

[45] At the time of his election, his party stated that Kernes would shortly return to Kharkiv to fulfil his duties as Mayor.

[50] His funeral ceremony was held at Kharkiv's Annunciation Cathedral in a service that was led by the primate of the Ukrainian Orthodox Church of the Moscow Patriarchate, Metropolitan Onufriy.

[51] Kernes owned 27 dogs, assorted birds, and other animals and since 2007 had lived in a Kharkiv hotel.

[11] Since they met in 1998, Kernes was a close friend of Mykhailo Dobkin – governor of Kharkiv Oblast from 2010 to 2014, mayor of Kharkiv from 2006 to 2010, past member of the Verkhovna Rada (Ukraine's parliament) and the Party of Regions candidate in the 2014 Ukrainian presidential election.

[55][56] A video (containing swearing) leaked in 2007 of Kernes instructing Dobkin is famous in Ukraine and has created a few national catchphrases.