J50 has not been seen since last Friday. The last known sighting of the 3-year-old orca was on September 7, researchers said.
Researchers blame the decline on multiple factors including pollution, boat noise and a shortage of Chinook salmon, the orcas' preferred food.
Whale experts feared the orca was dead earlier this month when J50 lagged behind her family and went missing.
"We're watching a population marching toward extinction", Ken Balcomb of the Centre for Whale Research said on Thursday.
She was also not seen on Thursday, where 60 whales from J, K, and L pod were seen off Oak Bay and near Race Rocks.
The Center for Whale Research said that the orca and her group became separated from the main pod somewhere in the Strait of Juan de Fuca. As teams scrambled to find her on Thursday, she failed to appear with her pod once again, despite favourable sighting conditions.
Officials were searching for the almost four-year-old whale in the water yesterday.
The southern resident killer whales, which are so endangered there are just 75 individuals left, swim between Canadian and US waters to Seattle and Vancouver ports through busy shipping lanes.More news: Landslide at Greek beach on Zakynthos caught on camera
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The high-profile cases have focused global attention on the plight of southern resident killer whales, whose numbers have dwindled to 75 and now - if J50 has died - to 74 in three pods.
J50 is seen in 2016 with its mother J16.
Scientist began to be concerned about J50 in July.
He believes she died between last Friday and Monday.
"This is a very sick whale", Joe Gaydos, a wildlife veterinarian with the SeaDoc Society involved in the effort to save J50, told the AP. "Teams were on the water searching yesterday and are increasing a broad transboundary search today with our on-water partners and counterparts in Canada", NOAA Fisheries spokesperson Michael Milstein said. The West Coast Marine Mammal Stranding Network was also activated, and airlines flying in and out of islands in the area were on the look out.
"She was like this little Energizer bunny that just keeps going and going, and definitely captured our hearts", he said.
The message, the Center for Whale Research said in a website post, is that extinction is looming "while the humans convene task forces and conference calls that result in nothing, or worse than nothing, diverting attention and resources from solving the underlying ecological problems".
J50's likely death is just another sign of the perilous situation the southern resident killer whale population is facing.