In a state long attuned to the drumbeat of political corruption — salacious charges, furious denials, explosive trials — Senator Robert Menendez has often registered as the quintessential New Jersey politician.

He successfully avoided charges in one case, and after federal prosecutors indicted him in another, he got off after a mistrial in 2017. “To those who were digging my political grave,” Mr. Menendez warned then with characteristic bravado, “I know who you are and I won’t forget you.”

Six years later, he is once again on the brink, battling for his political life after federal prosecutors in Manhattan unsealed a jarring new indictment on Friday charging the powerful Democratic senator and his wife in a garish bribery scheme involving a foreign power, piles of cash and gold bars.

A defiant Mr. Menendez, 69, immediately vowed to clear his name from what he cast as just more smears by vengeful prosecutors. A top adviser said that he would also continue running for re-election in 2024, when he is trying to secure a fourth full term.

But as details of the case quickly spread through Trenton and Washington — including images of an allegedly ill-begotten Mercedes-Benz convertible and cash bribes hidden in closets — it was clear Mr. Menendez may be confronting the gravest political challenge in a career that started 49 years ago in the shadow of New York City.

Calls for his resignation mounted from ethics groups, Republicans and even longtime Democratic allies who stood by him last time, including the governor, state party chairman and the leaders of the legislature. And party strategists and elected officials were already openly speculating that one or more of a group of ambitious, young Democrats representing the state in Congress could mount a primary campaign against him.

“The alleged facts are so serious that they compromise the ability of Senator Menendez to effectively represent the people of our state,” said Gov. Philip D. Murphy, a Democrat. “Therefore, I am calling for his immediate resignation.”

Representatives Frank Pallone and Bill Pascrell, two of the state’s longest serving Democrats who have served alongside Mr. Menendez for decades, joined them later. So did Representatives Mikie Sherrill and Andy Kim, two of the younger representatives considered possible primary challengers or replacements should the senator step down.

For now, Mr. Menendez appeared to be on firmer footing among his colleagues in the Senate, including party leaders who could force his hand. They accepted his temporary resignation as chairman of the Foreign Relations Committee, but did not ask him to leave office.

In a statement, Senator Chuck Schumer, Democrat of New York and the majority leader, called Mr. Menendez “a dedicated public servant” and said that his colleague had “a right to due process and a fair trial.”

Calls for his ouster seemed to only embolden Mr. Menendez, who spent part of Friday afternoon trying to rally allies by phone. “It is not lost on me how quickly some are rushing to judge a Latino and push him out of his seat,” he wrote in a fiery retort to Democrats who broke with him. “I am not going anywhere.”

The electoral stakes were high, and not just for Mr. Menendez.

Though he had yet to formally answer the charges in court, some party strategists were already gauging the possibility that Mr. Menendez could be scheduled to stand trial in the middle of the campaign — an unwelcome distraction for Democratic candidates across the nation.

Republicans were already using the indictment to attack the party. “Democrats covered for Menendez the first time he got indicted for corruption,” said Philip Letsou, a spokesman for the Senate Republican campaign committee. “It would be a shame if they did so again.”

Democrats have not lost a Senate race in New Jersey since the 1970s. But allowing Mr. Menendez to stay in office could at the least force the party to spend heavily to defend the seat at a time when it already faces daunting odds of retaining a razor-thin majority.

“I understand personal loyalty, and I understand the depths of friendships, but somebody needs to take a stand here,” said Robert Torricelli, the former Democratic senator from New Jersey. “This is not about him — it’s about holding the majority.”

Mr. Torricelli speaks from experience. He retired rather than seek re-election in 2002 after his own ethics scandal ended without charges. He was also widely believed to be a target of Mr. Menendez’s ire after the former senator put his hand up to succeed Mr. Menendez had he been convicted in 2017.

“In the history of the United States Congress, it is doubtful there has ever been a corruption allegation of this depth and seriousness,” Mr. Torricelli added. “The degree of the evidence. The gold bars and the hundreds of thousands of dollars of cash. It’s incomprehensible.”

The details laid out in the 39-page indictment were nothing short of tawdry. Prosecutors said that Mr. Menendez had used his position to provide sensitive government information to Egypt, browbeat the Department of Agriculture and tamper with a criminal investigation. In exchange, associates rewarded him with the gold bullion, car and cash, along with home mortgage payments and other benefits, they said.

Prosecutors referred to a text between an Egyptian general and an Egyptian American businessman in which Mr. Menendez was referred to as “our man.” At one point, prosecutors said, the senator searched in a web browser “how much is one kilo of gold worth.”

Mr. Menendez is far from the first elected official in New Jersey to face serious criminal allegations. With a long tradition of one-party rule, a bare-knuckle political culture and an unusual patchwork of governmental fiefs, the state has been a hotbed for corruption that has felled city councilors, mayors, state legislators and members of Congress.

The Washington Post tried to quantify the criminality in 2015 and found that New Jersey’s rate of crime per politician easily led any other state.

Mr. Menendez already has a Democratic primary opponent, Kyle Jasey, a real estate lender and first-time candidate who called the indictment an “embarrassment for our state.” But political strategists and elected Democrats said Mr. Jasey may not have the lane to himself for long.

New Jersey has a glut of ambitious Democratic members of Congress with outsize national profiles; it took barely minutes on Friday for the state’s political class to begin speculating about who might step forward.

Among the most prominent were Ms. Sherrill, 51, and Josh Gottheimer, 48, moderates known for their fund-raising prowess who have proven they can win difficult suburban districts and were already said to be looking at statewide campaigns for governor in 2025, when Mr. Murphy cannot run because of term limits. Other names included Mr. Kim and Tom Malinowski, a two-term congressman who lost his seat last year.

National Republicans cast their focus on Christine Serrano Glassner, the two-term mayor of a small community roughly 25 miles west of Newark, N.J., who announced this week she would run.

Mr. Menendez, the son of Cuban immigrants, was elected to his first local office at age 20. At 28, he donned a bulletproof vest as he testified in a corruption trial against his former mentor. He won the mayoralty of Union City, before moving onto the State Assembly, the Senate, the House of Representatives and, in 2006, an appointment to the Senate.

It was only a matter of months before he was in the sights of the U.S. attorney’s office of New Jersey. The senator was never charged, but the investigation became campaign fodder after the U.S. attorney, then Chris Christie, issued a subpoena to a community agency that paid rent to Mr. Menendez while getting lucrative federal grants.

Almost a decade later, federal prosecutors went further, making Mr. Menendez the first sitting senator in a generation to face federal bribery charges in 2015. They accused him of exchanging political favors with a wealthy Florida eye surgeon for luxury vacations, expensive flights and campaign donations.

A jury heard the case two years later and could not reach a verdict; the Justice Department later dropped the prosecution, but the bipartisan Senate Ethics Committee “severely admonished” him for accepting gifts while promoting the surgeon’s interests.

Even so, Mr. Menendez handily won his party’s nomination and re-election in 2018.

To longtime analysts of the state politics, though, Friday’s case crossed a new threshold.

“Even by New Jersey standards, this one stands out — how graphic it is, how raw it is,” said Micah Rasmussen, a seasoned Democratic political hand who now leads Rebovich Institute for New Jersey Politics at Rider University.

“There is a world of difference between not reporting a plane ride and having half a million in hundreds stashed around your house,” Mr. Rasmussen added. “By all rights, this should be the end of the line.”

Tracey Tully contributed reporting.