The defeated incumbents include three with decades of service in the Legislature: Rep. Rick Geist, R-Blair; Rep. Joe Preston, D-Allegheny; and Rep. Babette Josephs, D-Philadelphia.
In the six special elections held for seats that have been vacant since January, Democrat Ed Neilson won the district held most recently by former Rep. Dennis O'Brien, a Philadelphia Republican who was a moderate and had served as speaker under a Democratic majority.
The five other special elections did not change parties, with Democrats holding four and Republicans one.
House Democratic campaign chief Rep. Brendan Boyle of Philadelphia said the one-seat gain signaled problems for the Republican agenda in Harrisburg, where the GOP controls both chambers and holds the governorship.
"We had an outside shot of going six-for-six, but really, the goal from the start was to make progress and win five of the six," Boyle said. "So I'm very happy we were able to achieve that."
Republicans remain in firm control of the House, 111-92.
Boyle's Republican counterpart, Rep. Dave Reed of Indiana County, saw the results as a draw.
"The Democrats won the five seats they should have won, we won the seat we should have won," Reed said. As for the Philadelphia seat that flipped, he said it was likely to be moved for the 2014 election to fast-growing York County by a redistricting plan currently under consideration.
"Denny O'Brien's been voting with the Democrats for four years anyway," Reed said.
Geist, who has been in the House since 1978 and is chairman of the House Transportation Committee, recently won a major victory with House passage of a bill to govern public-private partnerships in building transportation infrastructure.
Reed said Geist's long voting record may have contributed to his loss.
"Certainly, when you've got a voting record that goes on for that long, it's tough to not look back and pick a dozen or so that, if taken in a vacuum, represent a not-so-pretty picture," Reed said.
Preston, first elected in 1982, is the ranking member of the Consumer Affairs Committee and a vigorous participant in floor debates. Josephs, who won her first term in 1984, is among the most reliably liberal members of the House and is the ranking Democrat on the State Government Committee.
Democratic Reps. Ken Smith and Kevin Murphy, both of Lackawanna County, also lost. Smith has been in the House for three terms, while Murphy is completing his second term.