The 41-year-old singer dedicated his performance to his wife Chrissy Teigen, as they continued to grieve their loss.
John sang 'Never Break' from 2020 album Bigger Love and as he sat behind the piano in the empty Dolby Theater in Los Angeles, he said: "This is for Chrissy."
His voice was close to cracking as he sang the poignant lyrics: "I'm not worried about us and I've never been. We know how the story ends. We will never break."
The awards ceremony had been postponed from April due to the coronavirus pandemic and was hosted by Kelly Clarkson.
She praised John and Chrissy's strength in light of the personal tragedy they had suffered.
Introducing his performance on the night, Kelly said: "He and Chrissy both have this warm way of inviting us into their world. The highs and the lows.
"My heart - obviously all of our hearts - go out to you both in this very difficult time.
"And I'm thankful that you continue to share your light and your talent with all of us."
After the performance, Kelly said the moment had been "very special" and was "possibly my favorite of the night."