Sen. Ben Nelson, the Nebraska Democrat who built an image as a moderating influence on his party, announced Tuesday that he will not seek reelection in 2012, improving Republican chances of winning the seat and taking control of the Senate in 2013.

The two-term senator and former governor said in a Web video that he wanted to spend more time with his family and look for other ways to serve the country.

“Therefore, I am announcing today that I will not seek re­election,” he said. “Simply put: It is time to move on.”

In the past decade in the Senate, Nelson has built one of the most conservative records of any Democrat in Congress, often irritating the party’s liberal base and causing repeated political headaches for Democratic leaders both on Capitol Hill and in the White House. He voted with Republicans on a range of issues from abortion, gay marriage and stem cell research to the Iraq war and campaign finance reform.

Despite that record, or maybe because of it, Democratic insiders understood that he represented the best chance Democrats had of wining in a state such as Nebraska, and the national Democratic Party spent more than $1 million in advertising this year trying to boost Nelson toward reelection.

Recent Democratic-sponsored poll­ing suggested that the ads were increasing the senator’s personal approval ratings, albeit slightly.

But Republicans also signaled they would be willing to spend heavily trying to defeat Nelson, by casting him as an enabler of President Obama, particularly after Nelson voted for Obama’s health-care bill.

While Nelson has often differed with his party’s position, he delivered the deciding vote for the health measure, Obama’s signature piece of legislation. Nelson negotiated some Nebraska-specific provisions into the law before he would agree to support it. Critics of the law have referred pejoratively to the deal that Nelson cut as the “Cornhusker Kickback.”

Early GOP advertising efforts have focused heavily on this arrangement, which included exempting his home state from paying billions in Medicaid expansion costs.

That vote was expected to make Nelson’s reelection a tough proposition, but questions remain about whether the GOP would have been able to field a candidate strong enough to defeat Nelson.

Those in the running for the GOP nomination are state Attorney General Jon Bruning, state Sen. Deb Fischer and state Treasurer Don Stenberg, a favorite of the tea party.

There has been some talk in recent weeks that the state’s popular governor, Dave Heineman (R), might also run, but he has shown little interest. Other possibilities, now that Nelson is out, include members of the state’s all-GOP congressional delegation, particularly Reps. Lee Terry and Jeff Fortenberry.

It was unclear who might replace Nelson on the Democratic side, as the Democrats’ bench in Nebraska is pretty thin. But former senator Bob Kerrey has been mentioned and would instantly give his party a fighting chance in a state where Obama took just 42 percent of the vote.

At the same time, Kerrey recently told a Nebraska politics blog that it is “highly unlikely” he would replace Nelson on the ballot. And he wasn’t elaborating Tuesday.

“Ben’s retirement is a huge loss for Nebraska,” Kerrey wrote from a trip to India. “I am very sad he’s leaving. That is as far as I am going (right now).”

Businessman Scott Kleeb, the 2008 Democratic nominee in an open seat race against now-Sen. Mike Johanns (R), said Tuesday that he “has no interest” in running again.

Democrats acknowledged on Tues­day that the announcement was a setback but argued that the race isn’t a lost cause.

Nelson’s seat, however, becomes one of two Democratic-held seats that Republicans can feel fairly confident of winning — victories that would give the GOP at least half the seats it needs to regain a majority in the Senate.

The GOP is also favored to win an open seat in North Dakota, where Sen. Kent Conrad (D) is retiring.

Republicans need to win four Democratic-held seats to win an outright majority, but they could have an acting majority if they win three and the presidency. In an evenly divided Senate, the vice president holds the tiebreaking vote.

Who controls the Senate in 2013 will be determined by the outcome of races in a handful of other states — Missouri, Montana, Virginia, Florida, Ohio, Massachusetts and Nevada — that both parties acknowledge are likely to be close.

Democrats now have less margin for error, but even Republicans acknowledge that Nelson’s seat was more of a stepping stone than a majority-maker.

The Nebraskan is the sixth Senate Democrat to announce his retirement. Two Republicans are retiring, along with independent and former Democrat Joseph I. Lieberman (Conn.).

Nelson is one of two Senate Democrats — the other is freshman Sen. Joe Manchin (D-W.Va.) — who often vote against their party’s leadership on big issues. In the House, the ranks of conservative “Blue Dog” Democrats were decimated in the 2010 election, and most of the remaining members are either retiring or facing tough races.

Staff writer Chris Cillizza contributed to this report.