Despised by some, admired by others, the U.S. has been the Middle East’s principal power for decades, providing its allies with guidance and protection.

Now, however, with Russia and Iran thrusting themselves boldly into the region’s affairs, that special role seems to be melting away. As seasoned politicians and diplomats survey the mayhem, they struggle to recall a moment when America counted for so little in the Middle East—and when it was held in such contempt, by friend and foe alike.

“It’s the lowest ebb since World War II for U.S. influence and engagement in the region,” said Ryan Crocker, a career diplomat who served as the Obama administration’s ambassador to Afghanistan and before that as U.S. ambassador to Iraq, Syria, Lebanon and Pakistan.

From shepherding Israel toward peace with its Arab neighbors to rolling back Iraq’s 1990 invasion of Kuwait and halting the contagion of Iran’s Islamic Revolution, the U.S. has long been at the core of the Middle East’s security system. Its military might secured critical trade routes and the bulk of the world’s oil supply. Today, the void created by U.S. withdrawal is being filled by the very powers that American policy has long sought to contain.

“If you look at the heart of the Middle East, where the U.S. once was, we are now gone—and in our place, we have Iran, Iran’s Shiite proxies, Islamic State and the Russians,” added Mr. Crocker, now dean of the Bush School of Government and Public Service at Texas A&M University. “What had been a time and place of U.S. ascendancy we have ceded to our adversaries.”