All eyes had been on O'Brien's other runner, Santa Barbara – but it was the bigger-priced filly who grabbed the glory at Newmarket, taking the Ballydoyle trainer's tally in the race to seven, with five of those victories in the last six years.
Sent off at 10-1, Mother Earth was given a vintage ride from Dettori, who was registering his fourth win in the race.
The 50-year-old had her in mid-pack, behind Ryan Moore on Santa Barbara in the early stages, as Statement and Fev Rover made the running.
When Dettori asked Mother Earth to make his move, the daughter of Zoffany responded with a decisive turn of foot that took her into the lead.
They maintained the gallop and went on to score by a length from Saffron Beach, with Fev Rover a neck away in third and Santa Barbara (5-2 joint-favourite) just a nose further back in fourth.
Alcohol Free, the other joint-favourite, was just behind Santa Barbara in fifth.
O'Brien said: "Mother Earth is a very good filly, always was.
"It was unfair to Santa Barbara to come (after one run), but we had to come. With a view to coming back for the Oaks, she had to run.
"Ryan said he would have liked to have waited longer, but he saw Frankie coming on his outside and he had to go.
"Santa Barbara was just green in the dip, but after having one easy run, it was a great run.
"We kind of felt coming here that she was going to learn as much as she would having three runs, but there was a risk doing it that she was going to get beaten.
"She's classy and would have learnt a lot for it. She has plenty of time now to get over it before the next day, hopefully.
"We never took her off the bridle at home – today was her first time. Hopefully she'll come out of it OK and it will do her good.
"Frankie's filly is a very consistent filly. She had a great run in America on her last run last year and she's very professional and did everything really well, so we're delighted.
"Santa Barbara was always going to go to the Oaks and Mother Earth was always going to come back to the Irish Guineas. That was the plan."
He added: "It's great to have Frankie, what can you say – he's an unbelievable rider."