Menendez, 70, and two businessmen based in New Jersey face charges in a bribery conspiracy case in Manhattan federal court, in a trial that could last five to eight weeks.
The senator’s wife, Nadine Menendez, has also been charged but will be tried separately.
All four have pleaded not guilty.
Menendez is up for re-election in November and if exonerated hopes to run for a fourth full term as an independent. But recent polls show he is deeply unpopular among New Jersey voters, and many Democratic senators, including Cory Booker, have called for him to resign.
The outcome of Menendez’s case could affect the Democrat's reelection prospects and help determine which party controls the Senate next year. Along with independents who caucus with them, they hold a 51-49 Senate majority.
In the Egypt-related charges, Menendez faces accusations of accepting hundreds of thousands of dollars in bribes from three New Jersey residents between 2018 and 2022, and of having used his "power and influence to protect, to enrich those businessmen and to benefit the government of Egypt."
The veteran Democrat, whose parents immigrated to the United States from Cuba, has previously denied that he had committed any crimes.
Prosecutors say Menendez helped defendant Wael Hana, an Egyptian- American businessman, obtain a lucrative monopoly on the certification of halal meat exports to the North African nation.
FILE — Wael Hana, the co-defendant with U.S. Senator Robert Menendez, leaves the federal courthouse in New York, on September 26, 2023.
Menendez also tried to help defendant Fred Daibes, a prominent New Jersey developer, obtain millions of dollars from an investment fund linked to Qatar's government, prosecutors said.
Menendez and his wife also face obstruction of justice charges. The alleged crimes occurred between 2018 and 2023.
A fifth defendant, Jose Uribe, pleaded guilty to bribery and fraud charges in March and agreed to cooperate with prosecutors.
Nadine Menendez's trial is scheduled for July 8. Her case was separated after her lawyers said she developed a serious medical condition that required a lengthy recovery.
Documents released last month showed that the senator, if he chose to testify, might blame his wife by disclosing marital communications that would "tend to exonerate" him but could incriminate her.
His lawyers said Menendez could explain what they discussed during dinners with Egyptian officials and offer his wife's explanation for why Hana and Uribe "provided her certain monetary items."
FILE - Nadine Menendez, wife of Senator Robert Menendez who is charged with bribery, leaves federal court, on October 18, 2023, in New York.
The senator's corruption trial is his second.
In 2017, a New Jersey federal judge declared a mistrial after jurors deadlocked on whether Menendez broke the law by providing help to a wealthy ophthalmologist, Salomon Melgen, in exchange for lavish gifts and political contributions.
Menendez became a senator in 2006. He had chaired the powerful Senate Foreign Relations Committee but stepped down last September after first being indicted.
While New Jersey's voting population leans Democratic, public support for Menendez collapsed following his indictment.
Fewer than one in six voters polled in March by Monmouth University and Emerson College Polling said they approved of Menendez's job performance. Even less said they would vote for him as an independent.
Several Senate seats held by Democrats or independents may be closely contested in November. A seat now held by West Virginia Democrat Joe Manchin, who is not seeking reelection, is expected to turn Republican.
Information for this article was sourced from Reuters and Agence France-Presse.