Mulki was summoned by King Abdullah II after the capital Amman and several other cities were rocked by demonstrations that drew thousands of people.
"Prime Minister Hani Mulki submitted his resignation to the king this afternoon during a meeting at the Husseiniyeh Palace and the king accepted the resignation," a government source told AFP.
The king asked Education Minister Omar al-Razzaz to form a new government, the source added.
Jordan, a key US ally, has largely avoided the unrest witnessed by other countries in the region since the Arab Spring revolts broke out in 2011, although protests did flare late that year after the government cut fuel subsidies.
A mostly desert kingdom with few resources, the country has seen prices of several basic goods and services like bread, fuel and electricity steadily rise over the past year.
The rallying cries by demonstrators for Mulki to step down came after the government adopted a draft income tax law and announced new price hikes based on recommendations by the International Monetary Fund.
Protesters had vowed not to "kneel" and earned support from trade unions as well as a majority of MPs opposed to the new tax.
The premier's meeting with the king came hours after around 5,000 people gathered outside Mulki's office in Amman, on the fifth consecutive day of protests.
James Dorsey, a Middle East analyst, warned that "cosmetic changes" like the prime minister's removal may not be enough to satisfy protesters.
On Saturday Mulki -- who had formed his government in May 2016 -- met with trade union representatives who demanded the income tax law be revoked, but they failed to reach an agreement.
There was no immediate reaction to Mulki's resignation from any of the 16 trade unions backing the protests.
"The tax bill will continue to hound the new government, whatever its policy, until the law is thrown out," said Jordanian political analyst Adel Mahmoud.
According to official estimates, 18.5 percent of Jordan's population is unemployed, while 20 percent is on the brink of poverty.
The Economist Intelligence Unit earlier this year ranked Jordan's capital as one of the most expensive in the Arab world.
Last month the government adopted a draft income tax law, yet to be approved by parliament, aimed at increasing taxes on employees by at least five percent and on companies by between 20 and 40 percent.
And last week it announced a new price hike for electricity and fuel, before revoking it under orders from the king following protests.
Security officials said Monday 60 people had been detained since the protests began.
"There are some irresponsible groups who left protests to cause violence, destroy property and assault police, which is unacceptable," said Major General Hussein al-Hawatmeh.
The IMF loan, intended to support economic and financial reforms, has the long-term objective of reducing Jordan's public debt from about 94 percent of GDP to 77 percent by 2021.
Ahmad Awad, head of the Amman-based Phenix Center for Economic and Informatics Studies, said "tax policies have weighed on household budgets".
"Almost half of young people do not find work and are therefore a very high risk to social and economic stability and security."
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