Eddie Jones had intended to pick Smith at fly-half for the Autumn Nations Series opener at Twickenham but with his training severely limited by the unspecified problem, he is forced to settle for a bench role.
Instead, Farrell will act as ringmaster in his first start in the position since facing Scotland in February, four Tests ago.
It is a frustrating development that a 22-year-old seen as England’s most likely general for the 2023 World Cup will be limited to a cameo role only, but Jones insists he will be on the pitch against Tonga at some point.
“Marcus hasn’t been able to train,” Jones said. “He just did some light training today [Thursday] and we anticipate he’s going to be able to train fully tomorrow.
“Therefore we decided to start with Owen and Marcus will finish for us.”
Including Tests for the Lions, Farrell will be winning his 100th cap and has the reassuring physical presence of Manu Tuilagi at inside centre as the destructive centre returns after an 18-month international hiatus caused by injury.
While Smith is unable to make the starting XV, fellow prospects Adam Radwan and Freddie Steward will continue their development in the back three after making debuts in the July romps against the USA and Canada.
Radwan, regarded as the fastest player in English rugby, features on the right wing after scoring a hat-trick in his only previous Test and Steward has overcome his own leg problem to feature at full-back.
It will be their first outings before a full-house at Twickenham and Jones has urged them to deliver on the promise shown in the Gallagher Premiership.
Jones said: “It’s what they expect from themselves that’s the really important thing. We want trademark games out of them.
“To play with a lot of effort and a lot of control and we want them, if they get the opportunity, to bring their special talents to the game.
“Both are coming through a summer series, have been back to their clubs, played well and then come into the more senior squad and continued to impress.
“Freddie’s a similar sort of player to Mike Brown, but a much taller version. Courageous in the air and good work rate around the field.
“Goodness me, if he can be as good as Mike Brown he’s going to be a good player.”
Ellis Genge is preferred to Joe Marler at loosehead prop and Tom Curry is given the No 8 jersey ahead of Alex Dombrandt, who is present alongside fellow Harlequins rising star Smith on the bench.
Curry made four starts at No 8 during the 2020 Six Nations and never fully convinced in the position as England searched for an alternative to the injured Billy Vunipola, who is now fit but out of favour.
But the 23-year-old still has the backing of Jones to make a success of his back row reshuffle.
“Since he first came into the squad in 2017, when he came in mainly as a defensive player, he’s evolved his game to include some running skills, passing skills and some linkage skills more importantly,” Jones said.
“Courtney is a pretty strong ball runner and Underhill is strong over the ball, so it will give Tom the chance to mix his game between running and linking and his defensive work. He’s got the ability to do that.
“There are two players in the world similar in that aspect – him and Ardie Savea. They’re both natural sevens but have got the capacity to be outstanding eights because they have the ability to carry the ball, to link and still do the defensive work.”