Aid groups have warned that a battle for the province could result in a level of bloodshed that is unprecedented even in a war already defined by abject suffering.
In a tweet, US President Donald Trump warned Syria and its Iranian and Russian allies that a "reckless" assault on the province would be a "grave humanitarian mistake."
But in a sign that Washington is largely resigned to the offensive taking place, the comments of senior US officials focused on how, not if, the battle should unfold.
On social media, the US ambassador to the United Nations, Nikki Haley, urged Syria and Russia not to use chemical weapons. In Athens, Marine General Joseph Dunford, chairman of the Joint Chiefs of Staff, told reporters that the United States wanted a humanitarian disaster to be "avoided."
Russian rhetoric on the coming battle has intensified in recent weeks, with Foreign Minister Sergei Lavrov describing the opposition fighters as a "festering abscess" that needs to be "liquidated."
The strikes come amid wider disagreements between Russia and Turkey over how to end rebel control in Idlib, where former al-Qaeda affiliate Hayat Tahrir al-Sham (HTS) dominates everything from the provincial capital to border taxes on trade and aid assistance.
Large swaths of Idlib - including Jisr al-Shughour - are controlled by HTS. Its fighters have stepped up a campaign of arrests in recent weeks, erecting a public gallows for prisoners it accuses of contact with the Syrian Government.
Turkey has sought a more quiet and protracted policy of containment and negotiation with militants there, analysts say, fearful of a more direct conflict that could bring violence to Turkish cities. Turkey also wants to avoid a new influx of refugees.
But Russia, a staunch supporter of Syria's Government, says Turkey has not done enough to confront the rebels in Idlib, where Turkish forces had acted as a guarantor of a de-facto ceasefire in the province.
In recent weeks, Russia has threatened an all-out military offensive by Syrian forces to retake the area. But it is Turkey that Russia wants to act, according to the Brussels-based International Crisis Group, because any humanitarian crisis resulting from an assault on Idlib would hurt Russia politically.
Russia, the Crisis Group says, is courting European nations to not only reopen diplomatic relations with Syria's Government but also invest in reconstruction.
"Russia has enabled brutal regime victories before," the report said. "But an Idlib offensive would come as Russia is arguing that Syria's war is winding down and involve humanitarian suffering on a scale likely unprecedented in the war - straining talks between Russia and the European Union regarding reconstruction aid to the breaking point."
Pro-government outlets suggested that many of Tuesday's airstrikes targeted positions controlled by the Turkistan Islamic Party, a group of Uighur Chinese extremists that has allied with HTS.
In Jisr al-Shughour, rescue workers and civilians described a rush to underground shelters as some families piled in cars and headed for the border.
"Every five minutes, there are new strikes," said a rescue worker, Dured Bash.
Monitoring groups said five children from a single family were killed in the Basatin neighbourhood of Jisr al-Shughour.
A photograph shared by the rescue group known as the White Helmets showed a young boy being carried from the rubble, his body limp and caked with dust as blood poured out of his head.
