Spurs need to get their top-four bid back on track by beating their rivals, who will be desperate for three points to keep the pace with Premier League leaders Chelsea
The Gunners make the short trip to their closest rivals needing three points to ensure they do not lose further ground to Chelsea in the Premier League title race.
Arsene Wenger's side currently trail the leaders by seven points, albeit with a game in a hand, and know a loss this weekend could well represent a fatal blow to their challenge for top spot.
The Frenchman will be seeking a response after Arsenal exited the Champions League in midweek courtesy of a 3-1 aggregate defeat to holders Bayern Munich.
Tottenham head coach Tim Sherwood, meanwhile, has come under increasing pressure in recent days.
A heavy 4-0 loss to Chelsea in the Premier League was followed by a 3-1 reverse at home to Benfica in the Europa League last 16, a result that has severely hindered their hopes of reaching the quarter-finals.
Sherwood appears to have shown signs of feeling the strain, openly criticising his players in the wake of the Chelsea game and then saying Benfica counterpart Jorge Jesus "lacked class" after Thursday's match.
Securing qualification for next season's Champions League now appears a stiff ask for Tottenham, who still have work to do to ensure they reach the Europa League once again, with Manchester United and Everton close behind in the league table.
Encouragingly for Sherwood, Arsenal have failed to win on their previous five league visits to White Hart Lane.
However, Arsenal have triumphed in each of the two meetings between the teams this season, winning the reverse league game 1-0 in September prior to a 2-0 success in the third round of the FA Cup.
After Arsenal were defeated 1-0 by Stoke City in their last top-flight fixture, Wenger has warned his team they can have no more "weak moments" this season.
Referring to his side's poor recent form at Tottenham, he said: "We have played two draws and three losses there [in the last five meetings]. It is a difficult ground to go to for everybody.
"After Stoke it was very important that we had a good result against Everton [winning 4-1 in the FA Cup], we had a good result even at Bayern [when drawing the second leg 1-1 in Germany], but [it remains important] that we continue and have no weak moments until the end of the season."
If history is anything to go by then Arsenal and Tottenham fans can expect plenty of action when the duo meet on Sunday.
The fixture has provided 125 goals in 43 Premier League encounters; only Liverpool versus Newcastle United has a higher tally with 126.
Arsenal, though, will be without Germany international Mesut Ozil, who sustained a hamstring injury in the Bayern draw, while Aaron Ramsey misses out after suffering a setback in his recovery from a thigh problem.
Jack Wilshere [foot] also remains sidelined and Kieran Gibbs [calf] is doubtful, but Nacho Monreal [foot] returns and January loan signing Kim Kallstrom could make his long-awaited debut after returning to training following a back injury.
For Tottenham, full-back Kyle Walker and midfielder Sandro are both doubtful after coming off injured against Benfica, while Mousa Dembele [hamstring] could once more miss out.
Etienne Capoue [ankle], Vlad Chiriches [back] and Michael Dawson [hamstring] are also sidelined.