Wales set up a Grand Slam encounter against France in Paris next Saturday by clinically disposing of hapless Italy with a seven-try rout in Rome.
Hooker Ken Owens crossed for two tries with further scores from Josh Adams, Taulupe Faletau, George North, Callum Sheedy and Louis Rees-Zammit.
Italy only managed a try through wing Monty Ioane in response.
Wayne Pivac's side can complete the Six Nations clean sweep by winning at the Stade de France next weekend.
France and Scotland will still have a match to play after their third-round game was postponed because of coronavirus cases in the French camp.
But Wales have the chance to create their own 'Super Saturday' with victory at the Stade de France, where they could secure a second Grand Slam in three tournaments.
The omens are good. Wales have already won their fifth Six Nations Triple Crown since 2000 and on each of the previous occasions they have done so, they have gone on to seal the Grand Slam.
It represents a remarkable turnaround from a side that finished fifth in Pivac's first tournament in charge and managed only three wins in 10 games in 2020, although we have grown used to the boom-and-bust nature of Welsh rugby.
It might also be a special day for captain Alun Wyn Jones, who could become the first Welshman to celebrate four Grand Slams.
This was Wales' 16th successive victory over Italy, with the last defeat coming in 2007, and also represents their longest winning run against one opponent, overtaking a run of 15 victories against France from 1908-1927.
Relegation for Italy?
Another heavy defeat will again raise the inevitable questions about Italy's position in the Six Nations and whether there should be relegation, with the likes of Georgia being given the chance to join the tournament.
The facts are damning. It was a 31st successive defeat for the Azzurri in the competition with their last victory coming against Scotland in 2015. They have not managed a home Six Nations win for eight years, with 20 successive losses.
Italy have conceded 187 points and 26 tries in four games this year. Yet events off the field this week have actually strengthened their hand.
The £365m CVC private equity deal secures Italy's status as an equal partner for the next five years, with Six Nations boss Ben Morel saying the championship is "precious" and any changes "would need to be extremely carefully studied".
Dominant start
Before the match Pivac had warned not to expect any "razzle dazzle" from his Wales side, but that is exactly what the visitors provided in the Stadio Olimpico sunshine.
It was one-way traffic after Wales opened the scoring through a Biggar penalty before Italy captain Luca Bigi was yellow carded by referee Wayne Barnes for cynically stopping scrum-half Gareth Davies taking a quick tap-penalty.
Davies had been one of two changes in the Wales side for injured Kieran Hardy, who had scored from a similar move against England.
From the resulting scrum, Wales made their numerical advantage tell, as wing Adams, who claimed a hat-trick against Italy last year, dived over from a long Biggar pass. The fly-half converted.
Wales' dominance continued and searing breaks from Rees-Zammit and Adams allowed the visitors to move the ball in both directions before number eight Faletau crashed over as 12 points were scored with the extra man.
Wales also demonstrated their forward power when hooker Owens was driven over for his fourth international try from an attacking line-out.
Barnes then looked at television replays about a possible illegal tackle by Biggar on Italy flanker Johan Meyer.
The English barrister deemed there was no case to answer, although a later challenge by Biggar at the following ruck was not looked at.
The bonus point came in the 30th minute when Owens stretched over from another line-out for his second score.
Wales appeared to have scored a fifth try through Rees-Zammit but television match official Tom Foley picked up a final forward pass from Biggar as the visitors led 27-0 at half-time.
No mercy
The onslaught continued after the break with Jonathan Davies releasing co-centre North, who sprinted away to equal Shane Williams' Wales record of 22 Six Nations tries.
Italy responded with a fine individual effort from wing Ioane that Paolo Garbisi converted, while Adams was denied a second score after failing to ground the ball in time.
Wales made a raft of replacements, including Scarlets second-row Jake Ball coming on for his 50th cap before Italy replacement prop Marco Riccion was yellow-carded for dangerous use of the elbow.
Wales took advantage with a first international try for Bristol fly-half Sheedy before Rees-Zammit sped away spectacularly following an 80-metre interception to complete the scoring.
Man-of-the-match - Josh Navidi
Line-ups
Italy: Trulla, Bellini, Brex, Canna, Ioane, Garbisi, Varney; Fischetti, Bigi (capt), Zilocchi, Cannone, Sisi, Negri, Meyer, Lamaro.
Replacements: Fabiani for Ioane (7-18), Lovotti, Riccioni for Zilocchi (33), Lazzaroni for Cannone (52), Mbanda for Meyer (26-36), Violi for Varney (63), Mori, Padovani for Trulla (44).
Wales: L Williams; Rees-Zammit, North, J Davies, Adams; Biggar, G Davies; W Jones, Owens, Tomas Francis, Hill, AW Jones (capt), Navidi, Tipuric, Faletau.
Replacements: Dee for Owens (54), Carre for W Jones (57), Brown for Francis (45), Ball for AW Jones (54), Wainwright for Faletau (54), L Williams for G Davies (52), Sheedy for Biggar (52), Halaholo for North (46)
Match officials
Referee: Wayne Barnes (England)
Touch judges: Pascal Gauzere (France) & Christophe Ridley (England)
TMO: Tom Foley (England)