The Cuban government did not immediately respond to a request for comment on the sanctions, which also targeted four other people and five entities, including the Ministry of the Revolutionary Armed Forces of Cuba.
Diaz-Canel, 66, has served as president of the Caribbean country since taking over from Raul Castro, the brother of Cuba's former leader Fidel Castro, in 2018.
Thursday's action against Diaz-Canel is the latest by Washington to intensify pressure on the island's communist leaders.
The sanctions were announced as President Donald Trump told reporters the US wanted Cuba "to be a nicely run country."
Last month, the US government imposed sanctions on 11 Cuban officials, including the country's communications minister, several military leaders and its main intelligence agency.
The US also charged Raul Castro with murder for his alleged involvement in a 1996 incident in which Cuban jets shot down planes operated by a group of Cuban exiles.
Trump has ratcheted up talk of regime change in Cuba after pledging to conduct a "friendly takeover" of the country if its leadership did not open its economy to US investment and kick out US adversaries.
Secretary of State Marco Rubio has said Trump's preference is to reach a deal with the island's socialist leadership, but has said he is doubtful the US can reach a diplomatic resolution with the current government.
Last month, Rubio defended the Trump administration's decision to slap new sanctions on Havana, the largest of which is against Grupo de Administración Empresarial S.A., a business conglomerate operated by the Cuban Revolutionary Armed Forces.
Díaz-Canel was handpicked in 2018 to succeed Raúl Castro. He was the first person in decades to lead Cuba without bearing the name Castro.
Under him, the island plunged into the worst economic and energy crisis in recent history, a situation worsened by heightened sanctions imposed by the Trump administration.
Díaz-Canel's wife, Lis Cuesta Peraza, also appeared on the sanctions list. She does not hold the title of first lady, a title abolished in Cuba during the revolution, but in practice she acts as such, accompanying her husband on official trips.
Her son Miguel Anido Cuesta, who is Díaz-Canel's stepson, also faces sanctions.
with AP