Mickelson, whose wife was recently diagnosed with breast cancer, will be in the field for the first round Thursday and also plans to take part in next week's U.S. Open.
"I've never been this emotional, where if I'm driving alone I'll just start crying," Mickelson said during a news conference. "It's kind of a weird thing.
"I'm looking forward to having a four- or five-hour mental break where I force myself to focus on something else."
The world's second-ranked golfer opened his news conference with a statement in praise of Amy, to whom he has been married for 16 years.
"I think she's the most charismatic person I've ever met," he said. "She touches people in a way that people don't get touched. It's just right to the heart. She has a way to have an impact on people, the way she looks you in the eye, the way she listens to what you have to say, and genuinely cares."
In addition to the return of Mickelson to the PGA Tour, the St. Jude Classic will mark the first appearance on the circuit in more than six months for John Daly.
Daly was suspended by the tour for a series of events that were deemed inappropriate. He has lost 50 pounds during his absence and recently played three consecutive events on the European Tour. His best effort was a tie for second at the Italian Open.