First Lady Martine Moïse was hospitalised following the overnight attack, interim Premier Claude Joseph said in a statement on Wednesday.
The nation of more than 11 million people had grown increasingly unstable and disgruntled under Mr Moïse.
“The country’s security situation is under the control of the National Police of Haiti and the Armed Forces of Haiti,” Mr Joseph said in a statement from his office.
“Democracy and the republic will win.”
In the early morning hours of Wednesday, the streets were largely empty in the Caribbean nation’s capital of Port-au-Prince, but some people ransacked businesses in one area.
Mr Joseph said police had been deployed to the National Palace and the upscale community of Petionville and would be sent to other areas.
He condemned the assassination as a “hateful, inhumane and barbaric act” and said some of the attackers spoke in Spanish but offered no further explanation.
Haiti’s economic, political and social woes have deepened recently, with gang violence spiking heavily in Port-au-Prince, inflation spiralling and food and fuel becoming scarcer at times in a country where 60 per cent of the population makes less than US$2 ($2.66) a day.
These troubles come as Haiti still tries to recover from the devastating 2010 earthquake and Hurricane Matthew that struck in 2016.
Mr Moïse, who was 53, had been ruling by decree for more than two years after the country failed to hold elections, which led to Parliament being dissolved.
Opposition leaders have accused him of seeking to increase his power, including approving a decree that limited the powers of a court that audits government contracts and another that created an intelligence agency that answers only to the president.
In recent months, opposition leaders demanded he step down, arguing his term legally ended in February 2021.
Mr Moïse and supporters maintained his term began when he took office in early 2017, following a chaotic election that forced the appointment of a provisional president to serve during a year-long gap.
Haiti was scheduled to hold general elections later this year.