This was the most watched race in the country on Tuesday as voters continued to punish incumbents for the many failures of Washington.
It also marks another humiliating defeat for President Obama, who endorsed Specter.
Obama-supported candidates in Virginia, New Jersey, Massachusetts and now Pennsylvania have been rejected by voters.
From the wire service:
U.S. Sen. Arlen Specter has been defeated in a Pennsylvania primary in his bid for a sixth term after taking the risky step of switching to the Democratic Party.
Voters Tuesday picked U.S. Rep. Joe Sestak as the party's nominee and rejected the 80-year-old Specter in his first Democratic campaign.
With 65 percent of precincts reporting, Sestak received 339,402 votes, nearly 53 percent. Specter received 304,179 votes, about 47 percent.
The vote also was a defeat for President Barack Obama, who supported Specter when he abandoned the Republican Party last year.
The moderate Specter cast his switch as a decision of principle after inflaming the GOP by voting for Obama's economic stimulus bill. But many Democratic voters questioned his motives.
Sestak faces Republican Pat Toomey in the fall election.