The Democratic Party controls 192 seats.
"With his retirement announcement, Speaker Paul Ryan becomes the first casualty of the 2018 midterm election", tweeted House Democrat Gerry Connolly. He was also the Vice Presidential running mate for Mitt Romney in 2012.
After Trump became president in January 2017, Ryan often expressed annoyance at being asked to respond to various incendiary Twitter messages from the president but rarely offered direct criticism.
Rather than go down with the ship - or perhaps suffer the same fate as Tom Foley in 1994, the last sitting speaker to lose a re-election race - Mr Ryan is reserving his seat on a lifeboat.
During the 2016 election, Ryan chastised Trump over his racially tinged comments and his crude remarks about women, caught on an "Access Hollywood" tape. "It's fleeting. That inspires you to do big things".
I am really proud of what we have been able to do.
He said his decision is what's best for his family.
But it appears the 48-year old Ryan, who was effectively drafted to be speaker following the announcement that Republican John A. Boehner of OH would be stepping aside, will last a little less than three years in the job that he assumed October 29, 2015.
But for the next Republican leader, the alternative - just barely keeping the majority - could be even worse.
Ryan would be unlikely to publicize any planned departure because it could hurt his fundraising capacity on behalf of fellow Republicans and undercut his ability to make deals in the House of Representatives.
House Majority Leader McCarthy, a Republican from California known to be closer to Mr Trump, is expected to seek the Speaker post. "And clearly that's what she's intending on doing and they're raising a lot of money on their side. I have no reason to believe that's going to happen, I have assurances that it's not because I've been talking with people in the White House about it". Members of the ultra-conservative House Freedom Caucus griped that Ryan was too quick to compromise with Democrats.
"They won't wait for nine months", Meadows told reporters of his party.
We can't say for sure whether that's really Ryan's primary motive against seeking re-election in November 2018. Because Scalise has said that he won't seek the job if McCarthy wants it, McCarthy will likely emerge as the frontrunner if he announced that he wants the job. Instead, he said, it would be more of a referendum on President Trump.