All Blacks hooker Coles will make his first start in more than four months in what will be his 100th game for the Hurricanes when he leads them on to Ellis Park to face the Lions on Sunday morning.
Having finally shaken off the concussion symptoms that ruled him out of the Test series against the British and Irish Lions, Coles returned off the bench against the Brumbies in Canberra last week.
He impressed in the 35-16 quarter-final win and pushes Ricky Riccitelli to the bench, while reclaiming the captain's armband from TJ Perenara.
The other starting change sees fit-again Vince Aso back at centre, prompting a cascade of positional switches out wide.
Jordie Barrett drops to fullback, Nehe Milner-Skudder to the right wing and Wes Goosen to the left wing.
Goosen's retention means powerhouse Test number 11 Savea drops from the starting side, a decision which coach Chris Boyd said was based purely on form.
"We've talked through the year that at the back end of the season reputation counts for nothing and form will dictate selection," he said.
"We were keen to get Vince back in the midfield in conjunction with Ngani, where they've performed pretty well.
"It left three guys competing for two wing positions and we thought Wes and Nehe had the better form currently," Boyd said.
The Hurricanes have played the Lions 20 times previously winning 17 of those matches and losing three, but the teams have not met in 2017.
The two teams last played in the 2016 Super Rugby final at Westpac Stadium where the Hurricanes won 20-3 to win the club's inaugural title.
Fourteen of the Hurricanes match day 23 on Sunday took part in last year's final.