“I will be 68 years old at the end of this term and it’s time for me to say goodbye,” Mr. Johnson said during a brief news conference in Vermillion, S.D. After thanking his family and staff he added: “The Bible says that there is a time for every season under heaven. It is now our season to spend more time with our six grandchildren and in the state we love.” Mr. Johnson’s decision, coming on the heels of a spate of retirement announcements from Democrats, opens up a potential new opportunity for Republicans in the state that President Obama lost by a large margin last year. Further, the retirement of Mr. Johnson, a moderate who is chairman of the powerful banking committee, will open up that slot, should Democrats maintain a majority. His replacement could be critical as Congress continues to deal with regulatory issues. Senators Carl Levin of Michigan, Tom Harkin of Iowa, Frank R. Lautenberg of New Jersey and John D. Rockefeller IV of West Virginia, all Democrats, have said they will not seek re-election. Two Republicans, Senators Saxby Chambliss of Georgia and Mike Johanns of Nebraska, have also said they will not run. Republicans, who are hoping that 2014 will finally be their year after two opportunities to take back the Senate majority have slipped from their fingers, are eying Mr. Johnson’s seat eagerly. “South Dakota voters rejected the liberal agenda by nearly 20 points in 2012, and it’s a prime pick-up opportunity for Republicans regardless of whose name ends up on the ballot,” said Senator Jerry Moran of Kansas, who is chairman of the National Republican Senatorial Committee. Former Gov. Mike Rounds, a Republican, had already planned to challenge Mr. Johnson. Another possible contender would be Representative Kristi Noem, who came in on a Republican wave in 2010. Senator Michael Bennet of Colorado, chairman of the Democratic Senatorial Campaign Committee, thanked Mr. Johnson for making his decision early enough to allow his party to mount a strong defense of the seat. Mr. Johnson’s success has been a thing of wonder since almost the beginning of his Senate career. After serving in the House for five terms, Mr. Johnson was elected to the Senate in 1996, winning by two percentage points in an expensive race for the low-cost state. In 2002 he ran again, beating John Thune (who went on to win a Senate seat in 2004) by a mere 524 votes of more than 330,000 cast, and focused largely on agricultural issues, taking moderate positions along an array of issues. In 2006, just a month after ascending to new powers with his party’s victory, he suffered a brain hemorrhage from which he struggled to recover, threatening his party’s fragile majority. In 2008 he ran again and won after proving that, with slurred speech and the frequent use of a scooter to ferry him around the Capitol, he could still manage his Senate career. Among Democrats in South Dakota who could succeed him, the greatest speculation centers on Mr. Johnson’s son Brendan and former Representative Stephanie Herseth Sandlin, who was defeated by Ms. Noem and has kept a relatively low profile since but remains popular in the state. “I’ve not discussed in detail what comes next, whether it’s Stephanie or Brendan or whatever,” Mr. Johnson said, in response to questions about whom he would like to see succeed him.