Rubio spoke at the start of an annual meeting in the Philippine capital, Manila, with counterparts from the Association of Southeast Asian Nations who have expressed alarm over the resurgent war in the Middle East that has battered their region.
Despite Washington's preoccupation with the war, Rubio said "we're with ASEAN 100 per cent".
"If we create a precedent in the Middle East where a nation state can decide that they are going to control an international waterway, charge a toll and if you don't pay them, blow up your ships, we have created a very dangerous precedent which will repeat itself in other parts of the world, including in this region," he said on Wednesday.
Washington's top diplomat also renewed allegations that Iran has reneged on commitments under a failed peace deal.
Rubio said Iran "has been reaching out to the United States, both directly and indirectly, to engage in talks about settling the differences", but gave no indication that the US was considering returning to peace talks with Iran.
Top diplomats from the US, China, Russia and several other countries are in Manila to take part in at the ASEAN ministerial gathering.
Newly minted British Foreign Secretary Ed Miliband was arriving Wednesday, his office said.
Australian Foreign Minister Penny Wong underscored her country's concern over the renewed war in the Middle East, warning that "the situation could deteriorate further without much warning".
"We want to see an end to this war. We want to see a ceasefire. We want to see negotiations and we want the strait to be opened," Wong told a small group of journalists.
Over-reliance on fossil fuel imports from the Middle East has made Southeast Asia particularly vulnerable to the energy shock triggered by the Iran war, according to the International Energy Agency, which called the crisis a "stark wake-up call" for the region's energy security.
Rubio also met counterparts in the four-nation Quad partnership, which is made up of the US, Australia, India and Japan.
They discussed maritime and transnational security, among other issues, and issued a joint statement after the talks that reaffirmed their commitment to maritime security initiatives that seek to counter China's growing influence in the region.
During the meeting, Japanese Foreign Minister Toshimitsu Motegi voiced his strong opposition to any attempts to change the status quo by force in the region, including in the disputed South China Sea and East China Sea, where China's increasingly aggressive actions have sparked concern.
Wong echoed his concern, saying "we have real concerns about behaviour that is destabilising and risky".
The Trump administration has repeatedly criticised China's assertive actions in the South China Sea to the disadvantage of smaller claimant countries such as the Philippines.
The territorial disputes, which also involve Taiwan and ASEAN members Vietnam, Malaysia and Brunei, are high on the agenda of the talks.
"We reaffirmed the need to enhance mutual trust and confidence, exercise self-restraint in the conduct of activities that would complicate or escalate disputes and affect peace and stability and avoid actions that may further complicate the situation," the regional bloc's ministers said in a draft joint statement.
Rubio met separately with Chinese Foreign Minister Wang Yi in a tightly secured convention complex by Manila Bay.
