The United States on Friday carried out a series of military strikes against Iranian forces and the militias they support in seven sites in Syria and Iraq, marking a sharp escalation of the war in the Middle East that the Biden administration has for four months sought to avoid.

The airstrikes, targeting command and control operations, intelligence centers, weapons facilities and bunkers used by Iran’s Islamic Revolutionary Guards Corps Quds Force and affiliated militia groups, made good on President Biden’s promise to respond to a drone attack in Jordan on Sunday that killed three American soldiers and injured at least 40 more service members.

The military action also sought to send a message to Iran and the militias it backs that continued attacks on U.S. troops in the region and commercial ships in the Red Sea would draw a response.

The strikes hit more than 85 targets at different locations using more than 125 precision-guided munitions, according to a statement by U.S. Central Command.

“This past Sunday, three American soldiers were killed in Jordan by a drone launched by militant groups backed by Iran’s Islamic Revolutionary Guards Corps,” President Biden said in a statement. “Our response began today.”

Mr. Biden approved the strikes earlier in the week. He even telegraphed that they were coming when he told reporters on Tuesday that he had made a decision on the response to the drone attack on a remote outpost in Jordan. Middle East analysts said that many Revolutionary Guards trainers, fearful that they could be hit, returned to Iran this week while militia leaders are in hiding.

But U.S. officials made it clear that Friday night’s attacks were to be followed by more over the next days, weeks and perhaps even months. Two American officials said the United States also conducted cyberoperations against Iranian targets on Friday but declined to provide details.

The American response, Mr. Biden said in his statement Friday, “will continue at times and places of our choosing.”

“The United States does not seek conflict in the Middle East or anywhere else in the world,” he said. “But let all those who might seek to do us harm know this: If you harm an American, we will respond.”

American bombers hit targets at four sites in Syria and three sites in Iraq in a 30-minute attack, U.S. officials said. John F. Kirby, a National Security Council spokesman, told reporters Friday night that the Iraqi government had been notified before the strikes.

Mr. Kirby said the targets at each site were picked because they were linked to specific attacks against American troops in the region, and to avoid civilian casualties. He said he did not know if any Iranians or militia members were killed or wounded in the attack.

The point of the strikes, Mr. Kirby said, was about “taking away capability” of the militias to continue to strike American troops. “This wasn’t just a message-sending routine tonight.”

By avoiding targets in Iran, the White House and Central Command are trying to send a message of deterrence while controlling escalation. It is clear from statements from the White House, and from Tehran, that neither the United States nor Iran wants a wider war. But, as the strike in Jordan showed, with any military action comes the chance of miscalculation.

The Biden administration carried out what officials called a “tiered” response — striking multiple targets from the air. The Pentagon deployed two American B-1B bombers, which departed from Dyess Air Force Base, Texas, early Friday and made the more than 6,000-mile flight to deliver their payload of munitions from the skies over Iraq and Syria.

Sending B1-B bombers from American soil carried several advantages, officials said. The B-1Bs can carry dozens of precision munitions, allowing commanders in the region to keep their land- and carrier-based strike aircraft in reserve for follow-up strikes, a U.S. official said. Mideast countries housing American attack aircraft are increasingly reluctant to have their bases used for offensive strikes in Iraq, Syria and Yemen to avoid being perceived as supporting Israel. Striking sites in the Mideast with aircraft launched from the United States and refueled midair is a muscular show of global reach and capability, the official said.

“The beauty of the American bomber is we can strike anywhere in the world at a time of our choosing,” Lt. Gen. Douglas A. Sims, the director of the military’s Joint Staff, told reporters Friday night.

Officials said that the strike was timed for clear weather. While the military can strike when there is cloud cover, a clear evening allows a higher degree of confidence.

General Sims said that once it was daylight in Iraq and Syria on Saturday, military analysts would closely examine the targets struck. But he said the Pentagon felt confident the bombers had hit “exactly what they meant to hit.” Secondary explosions showed that the Air Force planes hit the ammunition depots they were targeting, he said.

In a statement later Friday, the spokesman for Iraq’s Armed Forces, Maj. Gen. Yahya Rasool, called the American action in Iraq “unacceptable” and “a violation of Iraqi sovereignty.”

With Friday’s strikes, the administration moved to a new phase in its efforts to manage the widening conflict, which was set off on Oct. 7 when the militant group Hamas attacked Israel, killing 1,200 people.

Israel’s retaliation since then has killed more than 26,000 people, most of them women and children, according to Gaza’s health ministry.

Mr. Biden and his top aides have been reluctant to take steps that could draw the United States into a wider war in an already hugely unstable region. “That’s not what I’m looking for,” he told reporters on Tuesday.

The leader of Iran’s Revolutionary Guards Corps, similarly, said on Wednesday that Tehran was “not looking for war,” either. And Kata’ib Hezbollah, one of the groups that U.S. officials say may have been responsible for the attack, made the surprising announcement on Tuesday that it was suspending military operations in Iraq, where it operates. But the Revolutionary Guards Corps leader also warned that Iran was prepared to respond if attacked.

With the latest strikes, that possibility is inching closer. Administration officials said Mr. Biden had little choice but to hit back after the strike in Jordan killed the three American soldiers, especially since their deaths came amid a steady stream of attacks from Iran-backed groups like the Houthis in Yemen and Kata’ib Hezbollah in Iraq. And now experts say there is a real fear that Iran could be drawn further into the fray.

Mr. Biden has been under pressure from Republicans at home to respond forcefully to the attacks in Jordan. But critics on Capitol Hill said on Friday that the president’s warnings of impending strikes allowed Iranian and militia commanders and advisers to flee.

“The Biden administration spent nearly a week foolishly telegraphing U.S. intentions to our adversaries, giving them time to relocate and hide,” said Senator Roger Wicker of Mississippi, the top Republican on the Armed Services Committee.

The U.S. strikes on Friday may be just the beginning of an extended series of attacks intended to damage or destroy Iran-backed militias’ ability to launch missiles, drones and attack drones at American troops in Iraq, Syria and Jordan. The militias have conducted at least 166 such attacks since Oct. 7, according to the Pentagon.

Mr. Kirby signaled that strategy when he said on Tuesday that it was “very possible” that the United States would carry out “not just a single action, but potentially multiple actions, over a period of time.”

The B-1B bombers were in the air on Friday when Mr. Biden attended the dignified transfer of the three soldiers killed in Jordan: Sgt. William Jerome Rivers, 46, Specialist Kennedy Ladon Sanders, 24, and Specialist Breonna Alexsondria Moffett, 23. Their remains arrived at Dover Air Force Base in Delaware on Friday. The Army Reserve said this week that it had posthumously promoted Specialists Moffett and Sanders to sergeant, and Sergeant Rivers to staff sergeant.