Taking to the stage solo at Lincoln Financial Field Stadium in Philadelphia on Saturday night, Sheeran spoke directly to his fans.
"I've had to take and make difficult decisions, and I am making mistakes and I'm so, so sorry for them," he said.
Sheeran apologised, saying he had tried to avoid being "a political commentator of any kind" but could no longer hide his feelings.
Although the October 7 attack by Hamas was "horrific," Sheeran said, according to Variety, adding, "what is happening in Gaza is catastrophic and unjustifiable, and disproportionate".
"I am honestly so grateful that you're here tonight with me," an emotional Sheeran told his fans.
Sheeran said he was having conversations about contributing to help "victims of these terrible times, and listening and learning because I do not know enough".
Sheeran's show marked his first performance since rapper Macklemore announced he had been removed as one of the tour's opening acts after saying "Free Palestine" at a show on September 5 show in New Jersey.
The tour's other supporting acts subsequently quit to show solidarity with Macklemore.
The controversy did not matter to people who spoke to Reuters before Sheeran took to the stage.
Joy VanRuler, a 55-year-old teacher from Pottstown, Pennsylvania, said she supports both artists.
"It doesn't need to be political," VanRuler said in an interview outside the stadium in Philadelphia. "It's about the music, and we support both of them and it's all good".
Dozens of pro-Palestinian protesters gathered near the concert venue ahead of Sheeran's performance.
Organisers said they were there to talk to people about the conditions on the ground in Gaza and to highlight local groups advocating for Palestinians.
Macklemore posted on Instagram last week 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.
Kraft said in a statement that Macklemore would not perform at those shows.
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 he said "Free Palestine".
"If those words cost me the stage, while turning the conversation back to Palestine, then it was the most successful tour I've been on," Macklemore wrote.
In an Instagram post on Tuesday, Sheeran said the promoter was responsible for removing Macklemore and that he has "personal views on this devastating conflict" despite being publicly apolitical.
"Those who come to my shows do not expect a political forum," Sheeran wrote.
with PA
