Wales-born Feyi-Waboso, (21) will line up on the right wing less than a year after playing for National League One side Taunton Titans.
The Exeter flyer, who has won two caps as a replacement, comes in for benched back Elliot Daly - a veteran of 67 Tests - after scoring a late try as a substitute during England's 30-21 defeat by Scotland in Edinburgh last month.
Borthwick has made three personnel changes and one positional switch following the Calcutta Cup loss, with full-back George Furbank keeping his place ahead of Freddie Steward in a team announced Thursday at England's training base in Bagshot.
Tommy Freeman switches from right wing to left wing as England, who finished third at last year's World Cup, look to return to winning ways following victories over Italy and Wales in the opening two rounds of the Six Nations.
Fit-again scrum-half Alex Mitchell is recalled after missing the Scotland defeat due to a knee injury, with Danny Care in line to win his 100th cap off the bench.
In the pack, Ollie Chessum moves from lock to blindside flanker in place of Ethan Roots, with George Martin now partnering Maro Itoje in the second row.
Defeat by Scotland ended England's hopes of a Grand Slam.
By contrast Six Nations champions Ireland, coached by former England dual code international Andy Farrell, will arrive at Twickenham knowing a bonus-point win would secure consecutive titles with a game to spare.
Ireland, who have won their last three Championship matches against England, are also bidding to become the first team in the Six Nations era to record back-to-back Grand Slams.
"Ireland are without doubt currently one of the best teams in the world, and we'll have to be at our very best against them on Saturday," said Borthwick.
"We've prepared well for what will be another classic Six Nations game at Twickenham."
Former England captain Borthwick acknowledged Harlequins scrum-half Care's looming landmark by saying: "I'd like to pay special tribute to Danny Care who will win his 100th cap at Twickenham on Saturday.
"Danny has been a tremendous servant to English rugby and reaching this milestone is an incredible achievement.
"He's a wonderful player and someone who always puts the team first."
England (15-1)
George Furbank, Immanuel Feyi-Waboso, Henry Slade, Ollie Lawrence, Tommy Freeman; George Ford, Alex Mitchell; Ben Earl, Sam Underhill, Ollie Chessum; George Martin, Maro Itoje; Dan Cole, Jamie George (capt), Ellis Genge
Replacements: Theo Dan, Joe Marler, Will Stuart, Chandler Cunningham-South, Alex Dombrandt, Danny Care, Marcus Smith, Elliot Daly
Coach: Steve Borthwick (ENG)
