Ireland were welcomed to Cardiff on Sunday to face Wales in the launch of their Guinness Six Nations campaign.
Wales gained an early 3-0 lead, as full-back Leigh Halfpenny slotted a fifth-minute penalty in front of the posts.
Wales flanker Dan Lydiate’s first international appearance in more then two years ended prematurely after he was forced off by a knee injury. The 33-year-old went down as he prepared to challenge Keith Earls for the loose ball and, despite attempting to continue, had to replaced by Josh Navidi.
Ireland’s task became considerably harder in the 14th minute when Peter O’Mahony was dismissed for a high challenge on Tomas Francis.
Flanker O’Mahony powered in and caught Francis in the head with an elbow, prompting referee Wayne Barnes to consult the television match official before producing a red card.
Minutes later, Halfpenny added another straightforward penalty to double Wales’ lead to 6-0.
Undeterred by losing a man, Ireland responded with a prolonged period of pressure, albeit without being able to find a way through a stubborn Welsh defense.
Both teams were then forced into further reshuffles as Wales center Williams and Ireland lock James Ryan went off for head injury assessments.
Ireland halved their deficit in the 29th minute after fly-half Sexton successfully converted a 35-metre penalty to make it 6-3.
Ireland continued to be the dominant attacking force and levelled the scores at 6-6 five minutes before the break, courtesy of another Sexton penalty.
Farrell’s men then remained on the front foot and deservedly went into half-time 13-6 ahead courtesy of a converted try from Tadhg Beirne.
Robbie Henshaw broke the Welsh line with a powerful surge and, after Van Der Flier was held up on the line, lock Beirne was on hand to power over, with Sexton adding the extras.
However, Wales seized on a string of mistakes from the visitors to cut the deficit early in the second half.
Sloppy play caused Ireland to concede possession, allowing George North to burst past Iain Henderson and Lowe to touch down wide on the right.
Halfpenny was unable to add the conversion, leaving Pivac’s men 13-11 behind.
Wales had pinned back their opponents since the restart and reclaimed the lead thanks to a second try of the afternoon, scored by Rees-Zammit.
The wing produced a diving finish in the right corner and Halfpenny this time made no mistake with the kick to put his side 18-13 in front.
Another penalty from Halfpenny gave Wales breathing space at 21-13 with 14 minutes remaining.
Ireland were deprived of skipper Sexton for the final 10 minutes of the game after he was forced off for a head injury assessment.
The 35-year-old was visibly frustrated as he trudged from the field having been caught in the head by the knee of Justin Tipuric.
Ireland set up an intriguing finale courtesy of a Billy Burns penalty, leaving the score 21-16 with eight minutes remaining.
Ireland, who twice comfortably beat their opponents in Dublin last year, travelled to the Principality Stadium having yet to record an away victory since the appointment of Andy Farrell.
Defeat to France in Paris ended Irish title hopes last year, while they also lost to defending champions England at Twickenham.
Wales were bidding to overcome their worst performance in the tournament in 13 years. The Welsh entered 2020 as Grand Slam champions, but finished fifth after losing four matches during a miserable start to the tenure of head coach Wayne Pivac.