In his victory speech, Tillis said his primary mission is now to defeat Democratic Sen. Kay Hagan in the fall. He said Sen. Harry Reid needs to be made irrelevant.
"Reid and Hagan have been an echo chamber for Obama's bad ideas," Tillis said.
Hagan cruised to victory Tuesday over two others vying for the Democratic seat.
In a statement, Hagan said Tillis gave tax cuts to the wealthy while teachers went without pay raises.
"Thom Tillis has spent his time in Raleigh pushing a special interest agenda that has rigged the system against middle class families," Hagan said.
Tillis held a strong lead over Cary obstetrician Greg Greg Brannon for most of Tuesday evening. Tillis received 45 percent of the vote with more than one-third of precincts reporting unofficial results.
Brannon was second at 26 percent, followed by Charlotte pastor Mark Harris with 18 percent.
In his concession speech, Brannon congratulated Tillis on his victory and said Hagan needs to be defeated in November.
"He worked very hard and the key is Ms. Hagan must come home, without a doubt," Brannon said.