In Massachusetts, Democratic Attorney General Maura Healey became the first woman to ascend to that state's highest office.
She also will be the country's first openly lesbian governor.
In Maryland, a state where 31 per cent of the population is Black, Democrat Wes Moore became the state's first African American to win an election for governor.
DeSantis, who won office by less than half a percentage point four years ago, was ahead of Democratic challenger Charlie Crist by 19 percentage points with 92 per cent of the expected vote counted.
DeSantis, 44, now is widely expected to seek the Republican presidential nomination in 2024.
That likelihood has already drawn the ire of Republican former President Donald Trump, 76, who has nicknamed him "Ron De-Sanctimonious".
Trump has said he would make a major announcement next Tuesday, when he is widely expected to declare his candidacy.
In all, 36 states will elect a chief executive in the US midterm elections on Tuesday, with the future of abortion rights and democratic elections at stake in competitive elections across the country.
The high stakes brought increased money and attention to the state-level races, which typically get overshadowed in midterm elections by the fight for control of Congress.
Elsewhere around the country, Democrats are fighting to keep control of governorships in Michigan, Pennsylvania and Wisconsin to maintain the power to veto any legislation by the Republican-controlled legislatures that might curb abortion rights and voting access.
Republican victories in those presidential battleground states and Arizona could have implications for the 2024 White House election.
The party's nominees have embraced Trump's false claims that the 2020 election was stolen.
In Arizona, which has one of the country's closest gubernatorial races, Trump-backed candidate Kari Lake has repeated his assertions about voter fraud and said she would not have certified President Joe Biden's victory in that state.
Her opponent is Arizona Secretary of State Katie Hobbs, a Democrat who rose to national prominence in 2020 when she defended Arizona's election victory for Biden.
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