Seven other states also held primaries in one of the biggest vote nights of the 2014 campaign season ahead of November's congressional mid-term elections in which Republicans are aiming to take back the Senate from President Barack Obama's Democrats.
But all eyes were on Mississippi, where the Tea Party movement poured outside funding into its best chance to oust an establishment Republican Senate incumbent.
The conservative movement that promotes small government and lower taxes has had a rough 2014 campaign season, mostly failing to oust mainstream Republicans including Senate Minority Leader Mitch McConnell.
With 95 per cent of precincts reporting, McDaniel was leading Cochran by half a percentage point in the Republican Party primary battle in Gulf coast Mississippi, one of America's poorest and most politically polarized states.
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But with neither man crossing the 50 per cent threshold in the multi-candidate race, McDaniel and Cochran were forced into a run-off to be held later this month.
Cochran did not speak to supporters last night.
McDaniel has seized on Cochran's old-school style of behind-the-scenes negotiating with opponents, a quality increasingly absent in a gridlocked chamber where a take-no-prisoners attitude has come to prevail.
Experts say McDaniel could claim the momentum going into the run-off, having survived a Mississippi mudfight that saw four McDaniel supporters arrested after one sneaked into a nursing home to take pictures of Cochran's wife, who is being treated for dementia.