Issa occupied one of the most vulnerable Republican seats after 2016, winning re-election by just half a point - in a district Hillary Clinton carried by more than seven points.
Rep. Darrell Issa, R-Calif., will not seek re-election in 2018, he said Wednesday.
His district consists of parts of San Diego and Orange counties that have a solid GOP constituency, due in part to the Camp Pendleton Marine Corps installation, but that polticial base has eroded as California has moved steadily toward Democrats.
More Republican incumbents have already said they will retire this year (18) than the number of Democrats who did so ahead of the 2010 midterm elections (11), which swept Republicans into power, according to a former Democratic campaign official.
Issa won re-election on 2016 by less than a percentage point.
Those activists have protested weekly outside Issa's Vista, California, district office - leading to a odd scene in May in which Issa stood on his rooftop, looking down at the protesters below.
Issa, who made a national name for himself as an Obama administration antagonist while leading a House investigative committee, will not seek another term, NBC News has confirmed. Hillary Clinton won the district by almost 7 points in the 2016 election.
"After passing a devastating tax scam and fighting to rip away healthcare from millions of families, California Republicans clearly see the writing on the wall and realize that their party and its priorities are toxic to their re- election chances in 2018".
California holds a jungle primary, which means the top two finishers - regardless of party - advance to the general election.
"The Republican agenda in Washington has been a direct attack on Californians", DCCC spokesperson Drew Godinich said in a statement.