Omar, the frequent target of political insults from President Donald Trump, was uninjured. A security guard immediately grabbed the man and took him to the ground, according to a Reuters witness and video of the town hall event.
Police said they arrested the man for third-degree assault.
In her remarks, Omar was criticising ICE and Department of Homeland Security Secretary Kristi Noem, demanding that Noem resign after the recent shooting deaths of two US citizens in Minneapolis during Trump's immigration enforcement surge.
"ICE cannot be reformed, it cannot be rehabilitated, we must abolish ICE for good, and DHS Secretary Kristi Noem must resign or face impeachment," Omar said, to applause.
Moments later, a man seated in a front row stepped toward her and sprayed her with the contents of what police described as a syringe, telling Omar, "You must resign."
Omar defiantly took a few steps toward him, with her hand raised, before he was subdued.
She continued her remarks after a short break, resisting associates' urging to seek medical attention, saying she just needed a napkin. Her office later issued a statement saying she was OK.
Forensic scientists were gathering evidence at the scene, Minneapolis police said in a statement.
A Reuters witness said the liquid smelled of ammonia and caused minor throat irritation.
"I learned at a young age, you don't give in to threats," Omar told the audience, after refusing to suspend the event. "You look them in the face and you stand strong."
Trump has repeatedly targeted Omar in public remarks and social media posts, also taking aim at her Somali nationality.
"Ilhan Omar is garbage," Trump said during a cabinet meeting in December. "She's garbage. Her friends are garbage."
Omar, 43, came to the United States as a 12-year-old girl and became a US citizen in 2000.
