Mickelson's participation was announced on Monday, with fellow American Tony Finau also joining the field for the Jan 30.-Feb. 2 tournament.
Defending champion Dustin Johnson, world number one Brooks Koepka and British Open champion Shane Lowry are among those previously confirmed to play.
"I am really looking forward to playing in Saudi Arabia in January," five-times major champion Mickelson said in a statement.
"I watched Dustin win the title last year and thought the course looked like an interesting challenge.
"Having so many talented players on show also made it look like a much more established tournament than one in its inaugural year."
The decision means Mickelson will miss the PGA Tour's Phoenix Open, a tournament he has played 27 years in a row, in the city where he went to university.
The Saudi International, to played on the Royal Greens Golf course adjacent to the Red Sea in King Abdullah Economic City, will offer prize money of $3.5 million, on top of undisclosed appearance fees paid to attract the top players.
The European Tour is strongly supporting the tournament, despite what Amnesty International describes as Saudi Arabia's "heinous human rights record."
"We will be back in Saudi and we'll continue to grow that event," European Tour CEO Pelley told Reuters earlier this year. "We believe our role will help the evolution of the country."
Mickelson echoed that sentiment on Monday.
"I have enjoyed my previous visits to the Middle East and am looking forward to playing in a new country and doing my bit to grow the game in the Kingdom," he said. (Reporting by Andrew Both in Cary, North Carolina Editing by Christian Radnedge)