Rick Warren preached from the pulpit on Saturday for the first time since the death of his son in April.
Matthew Warren had battled for many years with mental health before taking his life in his Mission Viejo home on 5 April.
The 16 weeks since his son's suicide is the longest absence Pastor Warren has had from the pulpit.
He preached at two Saturday evening worship services at the Saddleback Church, in Lake Forest, California, attended by more than 10,000 people.
He preached on "How to get through what you're going through" and was joined onstage by his wife Kay, who talked about choosing hope, reflecting the title of her 2012 book "Choose Hope".
They revealed their commitment to tackling the stigma of mental illness.
"Any other part of the body, you can have it hurt and there is no shame in it," Pastor Warren said. "If your brain doesn't work right, why do you have stigma? It's just another organ in your body."