Australia will be determined to end their tour with a morale-boosting win over England after a barren run against their rivals.
England will attempt to continue their dominance of Australia and in-form Wales host South Africa in another mouthwatering Test on Saturday.
The Wallabies have lost their last five matches against old rivals England and Eddie Jones will be desperate to send his compatriots home on the back of another defeat at Twickenham.
Wales have won eight consecutive matches, but they can expect a stern test from the Springboks in Cardiff.
Ireland ought to have far too much for the United States, while New Zealand should end their tour with a victory over Italy. Scotland host Argentina and France entertain Fiji in another busy day of international rugby.
With the help of Opta, we take a statistical look at this weekend's matches.
England v Australia
Australia have never suffered six straight defeats to England, so they will be out to avoid making unwanted history in the Cook Cup showdown.
The Wallabies will aim to secure back-to-back victories for the first time in over a year following a 26-7 defeat of Italy last weekend.
Australia have just four Test victories to their name in 2018; the last time they picked up fewer than five wins in a calendar year was in 1995.
Dylan Hartley is in line to make a record 56th international appearance at Twickenham, surpassing Jason Leonard's tally.
Ireland v USA
This will be the 10th Test meeting between Ireland and the USA, and the fourth to take place in Dublin, with Ireland winning each of the previous nine encounters.
Ireland recorded a 55-19 victory in their most recent clash against the USA in June 2017, a game in which James Ryan and Jacob Stockdale both scored debut tries.
The USA have won their last nine Tests. They had previously never won more than four games on the bounce.
Ireland have conceded just 14 penalties in their three games this month, with their average of 4.7 penalties per game the lowest of any Tier 1 nation in November. No other side has conceded fewer than seven on average.
Italy v New Zealand
The All Blacks have won all 13 encounters with Italy, scoring at least 50 points in nine of those matches.
After losing to Ireland last weekend, the world champions will now be out to avoid consecutive defeats for the first time since August 2011.
Italy's Sergio Parisse is set to move clear of Gethin Jenkins as the fourth most-capped player in history (both currently have 134 caps). He will also become the second most-capped forward behind Richie McCaw (148).
Italy have lost their last 14 games at Stade Olimpico; their last victory at the famous Rome venue came in March 2013, when they handed Ireland a stunning 22-15 Six Nations defeat.
Scotland v Argentina
Scotland have won six of their last seven Tests against Argentina, their solitary defeat in that run coming at the 2011 Rugby World Cup.
The Pumas have won just two of their last 14 away games and have not been victorious away to two Tier 1 sides in a calendar year since beating Italy and France in November 2014.
Huw Jones assisted Scotland's opening try in the loss to South Africa last weekend and has now been directly involved in 14 tries in his 18 Test appearances. No Scotland player has been involved in more in that time, but Stuart Hogg has matched the tally with seven tries and as many assists.
Seven of Scotland's tries in 2018 have come from their replacements. Only New Zealand have seen their bench players cross the whitewash more often this year (10).
Wales v South Africa
Only twice have Wales enjoyed longer winning runs in their Test history than the current sequence of eight (winning 11 from 1907-1910 and 10 in 1999).
The only Tier 1 nation to have spent less time in possession on average this year than South Africa (16 minutes 46 seconds) is Wales (16 mins 37 secs).
Wales have won their last three games against South Africa at the Principality Stadium, two of which were by a margin of six points or fewer.
No player has scored more points in 2018 than South Africa's Handre Pollard (118) – however Wales' Leigh Halfpenny has averaged 11 points per game this year, the second most of any Tier 1 player behind Beauden Barrett (11.5).