After David Durenberger announced he would not seek reelection, Rod Grams surprised many by announcing, just months into beginning his first term in the U.S. House, that he would run for the U.S. Senate. However, Grams faced opposition for the Republican party endorsement from State Senator Gen Olson, Bert McKasy (former chief of staff to David Durenberger), and Doug McFarland. During the party endorsement process, the Grams campaign closely aligned itself with supporters of Allen Quist, who was challenging incumbent Governor Arne Carlson for reelection in the 1994 Gubernatorial race. Weeks before the Republican Party’s state convention, McFarland dropped out of the US Senate race after endorsing Allen Quist for Governor and joining his ticket to become Quist’s Lieutenant Governor running mate. Later, McFarland threw his support behind McKasy in the US Senate Republican Party endorsement campaign. After numerous ballots at the convention in St. Paul, Rod Grams won the state Republican party endorsement against State Senator Gen Olson and Bert McKasy. Grams moved on to win the Republican primary against Arne Carlson’s Lieutenant Governor Joanell Dyrstad, who had been replaced as his running mate with State Senator Joanne Benson. In the general election against Democratic Farm Labor candidate Ann Wynia and Independence Party candidate Dean Barkley, Grams won a close election to become Minnesota’s next US Senator.

Rod Grams ran for re-election in 2000 as the incumbent, losing to Mark Dayton. During the campaign, Grams’ wife Christine Gunhus was revealed to have written anonymous disparaging emails about Grams’ potential Democratic rival, Mike Ciresi, from her home computer. She received a fine and suspended sentence for violating political advertising regulations. The Grams campaign also ran a commercial during the campaign featuring the mother of Rod Grams. The spot ended with Audrey Grans uttering, “Uffda, vote for Rod.” On September 4, 2013 it was announced that Rod Grams had been battling colon cancer since 2012 and was receiving hospice care at his home. He died on October 8, 2013 at his home in Crown, Minnesota, aged 65.