Casado's rival for the top job, Soraya Saenz de Santamaria, told journalists she was conceding the race ahead of the official result announcement after PP deputies cast their ballots in Madrid.
The appointment of Casado, a lawmaker who has promised “hope” with a generational revamp of the party, will be seen as a lurch to the right for the party.
He has taken a hardline stance on the Catalan independence crisis, calling for the addition of offences such as illegally calling a referendum to the criminal code to boost Spain's legal response to the secession threat.
“Dialogue doesn't work with those who want to break the law,” he said this week.
Casado is also against decriminalising euthanasia as promoted by the Socialist government and wants to lower income and corporation taxes.
He will have to breathe life into a party which lost three million voters between the 2011 general elections, when Rajoy won an absolute majority, and the last polls in 2016.
Many have migrated to Ciudadanos, a centre-right party, angry over the series of corruption scandals that hit the PP in recent years.
Rajoy's ousting was partly seen as a censure for his handling of the Catalan independence crisis, and a perception that he was weak on rooting out graft.
After an acrimonious campaign that saw mystery videos released attacking both candidates, 3,082 delegates cast their ballot for the successor of Rajoy, who spoke for the last time as PP leader on Friday.
In a long, emotional speech, the 63-year-old who had bean a major figure of Spanish politics over the past 14 years asked PP members to “be responsible in carrying out your duties”.
Rajoy, who has long been one of Spain's great political survivors — he even walked away from a 2005 helicopter crash with just a broken finger — oversaw the country's economic recovery, though unemployment has remained stubbornly high during his tenure.
In May, a court announced it had sentenced former PP officials, businessmen and their spouses to a total of 351 years in jail for their role in a vast bribery scheme known as the Gurtel case.
It proved to be one corruption scandal too many for the PP, which has been hit by a series of graft accusations, and Rajoy was gone a week later.
Santamaria, 47, who served for six years as Rajoy's deputy, emphasised her experience ahead of the vote, painting herself as the only candidate with sufficient gravitas to defeat current Socialist Prime Minister Pedro Sanchez
in 2020 elections.
The PP, which still holds the most seats in parliament even if it lost its absolute majority, will have to rapidly prepare for municipal, regional and European elections in May 2019.