Case conceded the race when returns showed he trailed by a margin of 55 percent to 45 percent with roughly two-thirds of the expected vote counted. Akaka had 87,102 votes compared to Case's 71,712.
"Losing is never easy," Case said in his concession speech. "It doesn't mean the ideas we put forward in this campaign are not valid."
Who Akaka faces in the general election remained a mystery after former Vietnam prisoner of war Jerry Coffee, who pulled out of the race because of health reasons, won the GOP nomination. Republicans have three days to name a replacement candidate.
Akaka, 82, has served in Congress for 30 years and drew on his experience to boost his candidacy.
"I want to thank Hawaii for supporting me all these years," he said. "It has been a tough campaign for me."
Case, 53, who did not win on any of Hawaii's islands, had argued that Hawaii needed a younger, more moderate senator.
He faced the difficult challenge of unseating Akaka, who campaigned on his consistent votes against the Iraq war and his congressional seniority as reasons voters should back him.
While the Senate race attracted the most interest, voters also picked candidates for Hawaii's two congressional districts, governor, and state and local positions.
In the governor's race, former state Sen. Randy Iwase won the Democratic gubernatorial nomination over Hawaiian activist William Aila. Iwase will take on Republican Gov. Linda Lingle, but she is expected to easily win a second term.
The race for Case's congressional seat developed into a free-for-all, with a dozen experienced candidates seeking the nomination.
Former Lt. Gov. Mazie Hirono held a lead late Saturday over state Sen. Colleen Hanabusa in the 2nd Congressional District, but Hanabusa was ahead on vote-heavy Oahu with two-thirds of the vote still out. The primary winner is favored to win the general election, keeping Hawaii's congressional delegation all Democratic.
Democratic-leaning Hawaii has never unseated an incumbent member of Congress since it became a state in 1959, but Case had centered his campaign around the idea that voters need to boot Akaka in favor of a more youthful representative who can start to build up seniority.
Some voters leaving the polls Saturday who supported Akaka said they valued his seniority and consistent record.
"Experience does matter. I didn't like the dirty comparisons" that Case made in TV ads, said Ted Awaya of Honolulu.
Others backing Case said they wanted a new face in the Senate.
"I think we need a change. We've been in a stalemate for too many years and we needed someone new," Nancy Clines said.
Akaka, who drew endorsements from leading Senate Democrats, held more than a 2-to-1 advantage in fundraising, collecting more than $2 million to Case's $817,000 by early this month.
Hawaii has the lowest voter turnout in the nation, with even less participation in primaries. Only 40 percent of 626,000 registered voters cast ballots in the 2004 primary.