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 leader 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 trails the leaders by seven points, albeit with a game in a hand, and the Gunners know a loss this weekend could well represent a fatal blow to their challenge for the top spot.
Wenger will be seeking a response after Arsenal exited the Champions League midweek courtesy of a 3-1 aggregate defeat to Bayern Munich.
Tottenham coach Tim Sherwood, meanwhile, has come under increasing pressure in recent days. A 4-0 loss to Chelsea in the Premier League was followed by a 3-1 defeat at home to Benfica in the Europa League last 16, a result that has severely hindered Spurs' hopes of reaching the quarterfinals.
Sherwood appears to have shown signs of feeling the strain, openly criticizing 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, which still has work to do to ensure it reaches the Europa League once again, with Manchester United and Everton close behind in the league table.
Encouragingly for Sherwood, Arsenal has failed to win in its previous five league visits to White Hart Lane. However, Arsenal has 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 triumph in the third round of the FA Cup.
After Arsenal was defeated 1-0 by Stoke City in its last top-flight fixture, Wenger has warned his team that it 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 [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 teams meet Sunday. The fixture has provided 125 goals in 43 Premier League encounters; only Liverpool vs. Newcastle United has a higher tally with 126.
Arsenal, though, will be without Germany international Mesut Ozil, who suffered 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, fullback Kyle Walker and midfielder Sandro are 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.