Sarah Thomas completed the feat in just over 54 hours. The 37-year-old endurance swimmer underwent treatment for breast cancer in 2018.
The open water marathon swimmer from Colorado finished a swim of around 130 miles (210 kilometers) on Tuesday morning near Dover, the largest English Channel port between Britain and France.
"I just can't believe we did it," said Thomas in an interview with the BBC. "I'm really just pretty numb."
Thomas is the first to cross the English Channel four times consecutively. Four swimmers had previously managed to cross it three times without stopping.
Fellow endurance swimmer Lewis Pugh wrote in a congratulation post on Twitter, "Just when we think we've reached the limit of human endurance, someone shatters the records."
During the 54-hour swim, Thomas battled strong currents, salt water that left her mouth and throat in pain, and a jelly fish sting to the face. For sustenance, every half hour her team threw her a protein drink tied to a rope.
While the planned route would have been roughly 80 miles, if taking the shortest crossing each time, the strength of the current pushing her off course meant that she actually covered roughly 130 miles.
The athlete previously set another record in August 2017, when she completed an unprecedented 104.6-mile non-stop solo swim in Lake Champlain on the U.S.-Canada border. Four months later, she was diagnosed with an aggressive form of breast cancer.
"I was at the peak of my athletic accomplishments...and then I got diagnosed with cancer," Thomas said in a video posted online. "I just hope it never comes back but if it does, to know that I did everything I wanted to do in life."
She underwent treatment for the disease, which had already begun to spread, last year.
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Thomas dedicated the swim to all cancer survivors in a post on social media prior to the swim.
"This is for those of us who have prayed for our lives, who have wondered with despair about what comes next, and have battled through pain and fear to overcome," she wrote.