El-Sayed, a 41-year-old doctor whose campaign focused on healthcare, the economy and an end to unconditional military aid to Israel, is the first progressive to win a statewide primary in a US state that President Donald Trump carried in 2024.
He will face Republican former congressman Mike Rogers in November's midterm elections.
Democrats, who had been deeply divided between El-Sayed and his more moderate opponent, US Representative Haley Stevens, rushed on Wednesday to portray the entire party as behind him.
Senate Minority Leader Chuck Schumer, who had endorsed Stevens, said Democrats would unify to defeat Rogers; Stevens herself vowed to help El-Sayed win.
"Whatever differences that we might have had in the primary, they pale in comparison to what unifies us," El-Sayed said.
While Democrats have racked up a series of electoral victories since Trump returned to office last year, the Michigan contest again highlighted a central debate that has riven the party: whether to back progressive insurgents who have harnessed the left wing's anti-establishment anger or moderate candidates who can appeal to swing voters.
Republicans wasted little time in attacking El-Sayed as too extreme for Michigan.
Digital advertising from the party's Senate campaign arm and an allied super PAC described El-Sayed as "dangerous" and "the most radical Senate candidate in America."
Trump said on social media that El-Sayed's victory was "great news" for the Republican Party.
In a statement, Rogers wrote, "The choice this November is simple: common sense or complete insanity."
Stevens supporters had argued for months that she was better positioned to win the general election in a state that Trump has won twice in the last three presidential elections.
El-Sayed's backers, meanwhile, said his grassroots campaign had energised liberal voters as well as young people who are often disillusioned about politics.
The primary election drew the highest turnout for any Democratic contest in state history, according to the state party chair.
The Michigan race is essentially a must-win for Democrats, who are facing an uphill battle to win a Senate majority in November. The party must hang onto seats in battlegrounds Michigan and Georgia while also flipping four Republican-held seats, including at least two in states that Trump won by double-digit margins in 2024.
El-Sayed has work to do to mend fences after narrowly winning a bruising, divisive campaign in which he did not reach 50 per cent of the vote.
Will Marshall, president of the centrist Progressive Policy Institute think tank, said the election results show Stevens performed better in counties with large working-class and Black populations, while El-Sayed prevailed among white college-educated voters.
The race also served as a battleground between progressives and moderates over support for Israel, an issue that has played out in Democratic primaries this year.
Stevens benefited from tens of millions of dollars in spending by a pro-Israel super PAC. But analysts said one significant factor in El-Sayed's favour was that Michigan is home to some of the country's largest Arab American communities, where hostility to Israel's war in Gaza runs deep. El-Sayed would be the first Muslim elected to the US Senate if he prevails in November.
