The two suspected jihadists were wanted for the murder of a soldier, two civilians and a policeman this week in the kingdom, state news agency SPA quoted a ministry spokesman as saying.
The operation was launched in response to a video shared on social media in which one of the two men appeared to shoot dead a man he had tied up, "at the request of the Islamic State group", he said.
Investigators alleged the two brothers -- IS followers -- had also killed two civilians and a policeman in Al-Shamli on the same day, the spokesman said.
The gunmen, who were hiding in a mountainous region near Al-Shamli, refused to surrender and opened fire on security forces who retaliated, killing one and wounding the other, who was detained.
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A policeman was caught in the crossfire and died.
Saudi Arabia is part of a US-led military coalition fighting IS in Iraq and Syria.
On July 18 the interior ministry announced it had disrupted a network linked to IS and made more than 430 arrests, foiling new attacks on Shiite mosques and a diplomatic mission.
Since May, IS has claimed four suicide attacks in Saudi Arabia.