MSNBC projected the former Massachusetts governor took the Show Me State from President Obama based on his lead in early returns. CNN said Romney led 57-41 with 48 percent of the votes in.
Romney had been expected to win the state.
Democratic U.S. Sen. Claire McCaskill fended off Republican challenger U.S. Rep. Todd Akin 52-41 with 47 percent of precincts counted, CNN said.
Akin's campaign took a heavy blow when he suggested women who have been raped have a biological defense against pregnancy.
In the race for governor, Democratic incumbent Jay Nixon bested his Republican challenger, businessman Dave Spence, 53 percent to 44 percent, CNN said.
The Democrats were looking to make inroads in the state Legislature, where Republicans held a 106-57 edge in the House and a 26-8 edge in the Senate.