The Brazil global and Firmino both came on at halftime and scored within three minutes, as Liverpool came from behind to win 2-1.
Coutinho equalised with 20 minutes to play before, two minutes later, Georginio Wijnaldum released Firmino to slam a stunning victor home from just outside the box.
Tiredness and likely injuries will surely catch up to players the more successful they are in the domestic cup and European competitions.
Simon Mignolet (Liverpool): The goalkeeper has taken plenty of flak this season but the Belgian was in inspired form today as he pulled off a couple of brilliant saves and even looked assured at the majority of set-pieces.
Speaking to BBC Sport after Liverpool's dramatic 2-1 win at Stoke, Klopp heaped praise on the much-maligned shot stopper.
Although his team selection appeared bewildering, with Divick Origi and 17-year-old Ben Woodburn leading Liverpool's attack, Klopp explained he thought it impossible to start with Philippe Coutinho, who had been suffering from illness, and Roberto Firmino.
"Job done, 63 points and I couldn't feel any better", he said after a victory that put Liverpool nine points clear of Arsenal in fifth, who have two games in hand. He told Liverpoolfc.com: "Then, half-time, it was a hard decision to make because it was not clear that Roberto and Phil would be ready for 45 minutes".
Stoke nearly made it 2-0 in the 51st minute when an terrible header from Wijnaldum obliged goalkeeper Simon Mignolet to foil Adam from point-blank range.
"We needed Simon Mignolet with two outstanding saves, the second one [from Berahino] was one of the best I have ever seen - the save of the year", the German said post-match.
"Philippe Coutinho lost three kilos in the past three days, which some people wish - but for a professional footballer it's not too cool".
"So he was now at a point where it was clear if we tried to bring him through 90 minutes it would cause us real problems".
"We've come through a tough period of fixtures".
The News Agency of Nigeria (NAN) reports that Liverpool, with this win, remain third in the English Premier League table.
In turning round the game, Coutinho and Firmino also raised eyebrows.