Speaking a day after meeting Chinese counterpart Wang Yi, where the two discussed laying the groundwork for a September visit to the US by President Xi Jinping, Rubio said co-operation with China would not come at the expense of Washington's close Asian partners.
"We're already present. We have a role, and we're not going to abandon our allies. We've made that abundantly clear," Rubio told reporters on Thursday.
"These are the two most powerful economies in the world, two large militaries, two nuclear powers. We have to have a relationship with China. We want it to be as positive as it possibly can be, but that won't come at the expense of our allies and our partners in the region, or our presence here either."
Rubio earlier joined the East Asia Summit in Manila and security-focused ASEAN Regional Forum, where foreign ministers stressed the need for closer engagement amid global threats and renewed and intensifying hostilities in the Middle East.
The war in Iran and the blockade of the Strait of Hormuz are a key concern in Asia and for the hosts, the 11-nation Association of Southeast Asian Nations, a bloc heavily reliant on Middle East oil.
Chair Maria Theresa Lazaro, the Philippines' foreign secretary, opened the forum against a "backdrop of profound geopolitical and geo-economic uncertainty", adding "no nation can address today's complex security environment alone".
The US military completed a 12th successive night of attacks on Iran on Wednesday, with Iranian-aligned Houthis claiming hits the following day on two Saudi oil tankers, in a blockade that threatens a second chokehold on global oil supplies in the Red Sea, alongside the Strait of Hormuz.
Rubio vented his frustration at diplomacy with Iran, which he said was "begging every day" to make a deal, but kept moving the goalposts at a time when it was suffering tremendous losses.
The security concerns in Manila were not confined to the Middle East.
Tensions have been simmering this week over the South China Sea, with a second encounter in the space of four days on Thursday between Beijing and US ally the Philippines, which Washington is treaty-bound to defend in the event of an attack on its vessels.
Beijing has an armada of coast guard ships throughout the South China Sea and claims sovereignty over almost the entire waterway, including parts of the exclusive economic zones of Brunei, Indonesia, Malaysia, the Philippines, and Vietnam.
China's coast guard on Thursday accused the Philippines of "provocative actions" and said it had thwarted an intrusion at the strategic Scarborough Shoal, which, according to Manila, included use of water cannon.
It came after an altercation on Monday between China's coast guard and Philippine navy personnel at another disputed reef 650km away, also in Manila's EEZ, prompting the countries to summon each other's ambassadors.
"The whole world saw it. It's disturbing," Rubio said.
"That's why we continue to reiterate our commitment to our treaty partners, but also our commitment to freedom of navigation and respect for territorial rights."
China's foreign minister Wang was not present for Thursday's plenary gatherings due to meetings in Kyrgyzstan.
A day earlier Wang had urged ASEAN countries to work with Beijing to ensure peace in the South China Sea and "resist the incitement of foreign forces".
