Mr Pelosi, 82, was left with a fractured skull and serious injuries to his right arm and hands.
The suspect is said to have demanded to see Mrs Pelosi after breaking into the San Francisco home.
President Joe Biden saw the attack as political and called it "despicable".
A 42-year-old man has been arrested on charges including attempted homicide. No motive is known.
Mrs Pelosi - who was on the other side of the country in Washington DC at the time of the assault - flew back to see her husband in hospital.
A spokesman for the senior Democrat said Mr Pelosi had been attacked in the early hours of Friday morning "by an assailant who acted with force, and threatened his life while demanding to see the Speaker".
He was admitted to Zuckerberg San Francisco General Hospital for an operation and doctors expect a full recovery, said Mrs Pelosi's spokesman, Drew Hammill.
In a news conference, San Francisco Police Chief William Scott said officers had responded to a call at around 02:27 local time (09:27 GMT) on Friday.
They found Mr Pelosi and the suspect - named by police as David DePape - struggling over a hammer, but it was wrested from Mr Pelosi by the intruder, who violently assaulted him with it. Mr Pelosi was bludgeoned at least once, said police.
The suspect was tackled and disarmed by officers. He had attempted to tie up Mr Pelosi "until Nancy got home", law enforcement sources told CBS News. He reportedly shouted "where's Nancy?" during the incident.
He is also facing charges of assault with a deadly weapon, burglary and several other felonies, Chief Scott said.
He said the suspect had gained access through a rear entryway to the four-bedroom Pelosi home in the upmarket neighbourhood of Pacific Heights. Footage shows a smashed glass door at the property.
Chief Scott told a Friday evening news conference that the alleged intruder was currently in hospital, though he declined to share details about his medical condition.
At the start of the break-in, Mr Pelosi told the intruder he needed to use the bathroom then made a secret 911 call on his mobile phone and left the line open, allowing a dispatcher to hear him talking to the suspect, reports the Los Angeles Times.
Chief Scott confirmed it was Mr Pelosi who had called police and that a quick-thinking emergency dispatcher had been "able to read between the lines" and send officers.
"This was not a random act," said the police chief of the attack. "This was intentional."
He added: "Everybody should be disgusted by what happened this morning." “Our elected officials are here to do the business of their cities and their counties and their states. Their families don’t sign up for this,” Scott said. “Everybody should be disgusted about what happened this morning.”
Forty-two-year-old David DePape was arrested on suspicion of attempted murder, elder abuse and burglary, and remained in the hospital late Friday, police said. Paul Pelosi underwent surgery to repair a skull fracture and serious injuries to his right arm and hands, and his doctors expect a full recovery, the speaker’s office said.
Biden quickly called Speaker Pelosi with support and later delivered a full-throated condemnation of the “despicable” attack that he said had no place in America.
“There’s too much violence, political violence. Too much hatred. Too much vitriol,” Biden said Friday night at a Democratic rally in Pennsylvania.
“What makes us think it’s not going to corrode the political climate? Enough is enough is enough.”
The nation’s political rhetoric has become increasingly alarming, with ominous threats to lawmakers at an all-time high. The House speaker and other congressional leaders are provided 24-hour security, and increasingly more other members now receive police protection. This, as crime and public safety have emerged as top issues for voters in the election.
In San Francisco on Friday, police were called at about 2.30 a.m. to the Pelosi residence to check on Paul Pelosi, said Scott.
Scott confirmed that the intruder gained entry through the rear door of the home, which is in the upscale Pacific Heights neighborhood. Investigators believe the intruder broke through glass-paneled doors, according to two people familiar with the situation.
Paul Pelosi called 911 himself after telling the intruder he had to use the restroom, where his phone was charging, according to another person familiar with the situation and granted anonymity to discuss it. The person said the intruder confronted the speaker’s husband shouting, “Where is Nancy?”
Scott said the dispatcher figured out there was “something more” than she was being told, resulting in a priority dispatch and faster police response. “I think this was lifesaving,” he noted.
Inside, police discovered the suspect, DePape, and Paul Pelosi struggling over a hammer, and told them to drop it, Scott said. DePape yanked the hammer from Pelosi and began beating him with it, striking at least one blow, before being tackled by officers and arrested, Scott said. The FBI and Capitol Police are also part of the joint investigation.
Police said a motive for Friday’s intrusion was still to be determined, but three people with knowledge of the investigation told The Associated Press that DePape targeted Pelosi’s home. Those people were not authorized to publicly discuss an ongoing probe and spoke on condition of anonymity.
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