The 50-year-old head of the Fundamentalist Church of the Latter-Day Saints (FLDS), was caught near Las Vegas after spending at least two years on the run.
He went into hiding after being charged in Arizona with sexual misconduct for allegedly arranging marriages between minors and older men. He is also wanted in Utah on charges of being an accomplice to rape.
Although placed on the FBI's Ten Most Wanted List three months ago, Mr Jeffs was eventually found as the result of a routine check by traffic police in Nevada.
His arrest means the breakaway Mormon sect, which has an estimated 10,000 members, must face the prospect of having its way of life examined in court.
The FLDS split from the Mormon Church more than a century ago after the latter renounced polygamy.
The isolated sect now dominates the towns of Colorado City, in Arizona, and Hildale, in Utah, less than a mile away. A compound in Eldorado, Texas, is also home to a growing community.
Members believe a man must marry at least three wives in order to ascend to heaven.
Mr Jeffs - who became leader, or prophet, four years ago on the death of his 98-year-old father, Rulon - is reputed to have between 40 and 70 wives and nearly 60 children.
The charges he faces revolve around claims he arranged marriages between older men and under-age girls.
Two years ago, five boys also launched legal action claiming they had been unfairly expelled from the community so elder members of the sect would have less competition for wives.
The authorities believe as many as 1,000 teenage boys have been forcibly separated from their families, faith and community chiefly on those grounds.
Life in the compounds is said to be closely controlled, with women obliged to wear 19th Century-style dresses and braided hair and the church deciding which wives to give or take away from the men.
While polygamy is illegal in the US, the authorities have reportedly been reluctant to confront the FLDS for fear of sparking a situation similar to the 1993 siege of the Branch Davidian sect in Waco, Texas, which led to the deaths of about 80 members.
Arizona's attorney-general Terry Goddard said the capture of Mr Jeffs - who had a $100,000 (£52,600) bounty on his head - had been down to "good luck and good policing".
The charismatic former teacher was "dangerous for a number of reasons", he told the BBC's World Today programme.
"He has been the leader of a large polygamist sect which has many, many allegations that young women, in particular, have been taken into plural marriages without their consent and way below the legal age," Mr Goddard said.
Officers who searched the Cadillac Escalade in which Mr Jeffs was travelling with a brother and one of his wives seized at least $54,000 (£28,400) in cash, 15 mobile phones, laptops, radios and three wigs.
Speculation has now begun about what may happen to the community should Mr Jeffs be found guilty and jailed.
Mr Goddard told a Phoenix radio station that the arrest marked "the beginning of the end of... the tyrannical rule of a small group of people over the practically 10,000 members of the FDLS sect".
Other observers suggest that, at the least, members may splinter into smaller groups, thus weakening the sect's influence over their thinking.
However, some who have had close dealings with the group predict that putting Mr Jeffs on trial could make him a martyr in the eyes of supporters.
Rod Parker, a lawyer who previously worked for the FLDS, told the Salt Lake Tribune newspaper that sect members would not "change prophets" just because he was in jail.
And former FLDS member Ross Chatwin told the paper he believed Mr Jeffs was likely to remain in control with the help of compound leaders in Nevada and Texas.
Observers note that there has been little sign of Mr Jeffs' grip on the sect waning during more than two years on the run.
An FBI agent's report that Mr Jeffs had complained of being the victim "of what he termed religious persecution" suggests the sect may simply see the arrest as yet another attack on its faith and close ranks.