Breaking his silence on the issue, the British singer decried Israel's treatment of Palestinians in Gaza as "unjustifiable".
"I've had to take and make difficult decisions and I am making mistakes and I'm so, so sorry," Sheeran told his audience in Philadelphia, where he performed for the first time since Macklemore was taken off the tour.
At the start of the concert Sheeran called the October 2023 Hamas attack that killed 1200 Israelis "horrific".
But he called Israel's subsequent war, which has killed thousands in Gaza and displaced almost all of the population, "catastrophic and unjustifiable and disproportionate".
Controversy has surrounded Sheeran since Macklemore posted on Instagram that New England Patriots owner Robert Kraft had told Sheeran that Macklemore would not be allowed to perform at Gillette Stadium in Foxborough, Massachusetts, where Sheeran has shows on September 25 and 26.
Macklemore said Kraft and other stadium owners had told Sheeran he would not be allowed to perform in their venues if Macklemore remained on the tour after saying "Free Palestine" during a September 4 concert in New Jersey. The tour's other supporting acts subsequently quit to show solidarity with Macklemore.
Performing for the first time since the incident unfolded, Sheeran told fans "I really didn't know whether this tour would be carrying on".
"I really didn't know whether I'd be even getting on stage again, whether I even wanted to be an artist at all," he said.
"In these situations, you really find out who your friends are, and it's been a weird week. I just feel like it happened very quickly."
Sheeran said he had tried in the past not to be a "political commentator" because he wanted his shows to be about "unity".
"I cannot hide how I feel about it anymore," he said.
Sheeran concluded the concert saying: "The world is a scary place right now. America is a scary place right now. This gives hope".
Ahead of the show, fans said they were sticking by the musician.
Kassandra Rivera from Philadelphia said: "Everyone has their own opinion and it's fine".
"I came here to have a good time and watch Ed Sheeran.
"I've been waiting a whole year to come and see him, so I'm excited to see the show."
Before the concert a small but vocal pro-Palestine protest was held outside the subway station that serves the stadium, several hundred metres from the venue.
Philadelphia resident Hillary Steinberg told the Associated Press she had received a refund for her tickets and attended the protest instead.
"I think all art is political, and all music is political, and so this choice - even though he was saying that he wasn't complicit - is a political choice."
with Reuters
