Wales will complete their first clean sweep in the tournament for seven years if they beat the Irish at the Principality Stadium in the 16:45 SA time kick-off, giving them a perfect springboard for the World Cup later this year.
If they fail, England could win their third title in four Six Nations campaigns under Australian coach Eddie Jones if they beat Scotland at Twickenham.
But if both Wales and England lose, reigning champions Ireland could retain their title if they gain a bonus point in beating the Welsh, giving coach Joe Schmidt his fourth success in six years in his final year as their coach.
Gatland has urged his players to seize their chance with both hands.
"I pride myself on the record I've had in big matches when it's really mattered," he said.
"We have spoken all week about embracing (the moment) and not running away from it.
"You get opportunities that come along in life and you have to take them with both hands.
"I have said to this group of players you might never get a chance like this again and you don't want to let those opportunities pass you by."
It will be Gatland's 50th and final Wales game in European rugby's showcase tournament, with the New Zealander to step down after the Rugby World Cup in Japan later this year.
Gatland's Ireland counterpart and fellow Kiwi Schmidt will be overseeing his 30th, and also final, Six Nations game.
Gatland, who named a side unchanged from the one that beat Scotland 18-11 last weekend, added: "I know Ireland want to come and spoil the party but we have a chance of realistically finishing first or third while Ireland will probably be second or third.
"We know what is at stake and the prize is massive."
England meanwhile wait in the wings, with their match against the Scots kicking off at 19:00 SA time.
Scotland have not won at Twickenham since 1983 and if that streak continues this weekend could see England sneak in and take the glory if Wales come unstuck against the Irish.
Jones, the former Australia and Japan coach, saw England's bid for a Grand Slam this season ended with a 21-13 loss away to Wales.
He said the support in both Cardiff and Twickenham on Saturday could play a crucial role in deciding the destination of the title.
"The support of your fans is also definitely a massive factor," Jones said.
"That's one thing the Welsh have got in their favour, haven't they? They've got a great Cardiff crowd and we've got a great Twickenham crowd.
"That's going to help us on Saturday in those tough moments. The players might not hear it but they feel that positivity."
In the opening match of the day, France will seek to record just a second victory in this year's tournament when they face winless Italy in Rome at 14:30 SA time.
Under-fire France captain Guilhem Guirado, who has admitted he was almost stripped of the armband after the 44-8 thrashing against England, said his side were desperate to make amends for their poor campaign.
"I'm waiting for rebellion. I feel we're going to have a big match," said Guirado.