Watford, beaten for only the second time in six matches, saw Troy Deeney’s penalty saved by Petr Cech, who registered the 200th Premier League clean sheet of his career to become the first keeper to reach that mark.
The win leaves the Gunners sixth, 12 points behind fourth-placed Liverpool, who are in the final Champions League spot.
However, Arsenal could still qualify for next season’s Champions League if they win the Europa League, and that competition affected Arsene Wenger’s team selection on Sunday.
With Arsenal holding a 2-0 lead against AC Milan and playing the second leg of their last-16 tie at home on Thursday, Wenger took a risk by making six changes.
Aaron Ramsey and Laurent Koscielny were rested, with Jack Wilshere only on the bench, but the gamble paid off for Arsenal.
Arsenal give their fans something to cheer about
Those Arsenal fans who had turned up were almost celebrating after only two minutes when Aubameyang was clean through, but he was denied by a fine save by Orestis Karnezis.
But the Gunners took the lead only six minutes later when Mesut Ozil’s free-kick from the left touchline was powerfully headed in by Mustafi.
Aubameyang, Ozil and Granit Xhaka were denied by Karnezis, before Aubameyang made it 2-0, collecting Mkhitaryan’s pass and taking the ball around the Watford keeper.
After Deeney’s penalty miss, Mkhitaryan added a third when he shot past Karnezis following Aubameyang’s pass for his first league goal for the Gunners.
With the Europa League on Wenger’s mind, the Frenchman was able to take Mkhitaryan off late on for Wilshere, although Mustafi is now a doubt for Thursday’s match after he limped off in the second half.
Pierre-Emerick Aubameyang has now scored three times in six matches for Arsenal since his £56m move from Borussia Dortmund in January
A day to forget for Deeney
Defeat keeps Watford 10th and nine points clear of the relegation zone. They have 36 points from 30 matches and, on this evidence, should have enough quality in their squad to ensure another season of Premier League football.
Richarlison shot wide, headed wide and also saw a free-kick pushed away by Cech, with Roberto Pereyra wasting the rebound by shooting over when unmarked six yards out.
The Hornets’ best chance of the game fell to captain Deeney after Pereyra had been fouled in the penalty area by a combination of Ainsley Maitland-Niles and Alex Iwobi.
However, Deeney, much to the delight of the home fans, had the resulting spot-kick saved by Cech.
After that match, he said: “There’s a reason they lost. It’s having a bit of cojones. Whenever I play against Arsenal, I’ll go up and think ‘let me whack the first one and see who wants it’.
“They all just backed off. For me as a player, I just think ‘happy days’.”
But Deeney, who had scored three times in his past four appearances, had a day to forget on Sunday as his penalty was too close to Cech in the middle of the goal, and the Czech saved it.
Cech ends long wait to reach landmark
That penalty save from Cech meant he kept his 200th Premier League clean sheet, but he had to wait a while for it to come as his 199th was back on 16 December in a 1-0 win against Newcastle.
“We took 18 games [of this season] to get to nine clean sheets, I got to 199 and then had to wait 11 games to get another clean sheet,” said Cech.
“It was a bit frustrating but we now have eight games left and we have to make sure we win most of them. I believe I got this far through my work ethic.”
Wenger paid tribute to the 35-year-old and said: “It has highlighted what Petr Cech has done in his career, 200 clean sheets is remarkable and he has saved a penalty on top of that. It is quite fortunate that it was against Deeney.
“His [Cech’s] situation shows how football is, in one week he has gone from hell to heaven.
“A record like that needs a lot of motivation and a huge level of intelligence because you don’t last that long in the game if you’re not intelligent.”
Man of the match – Henrikh Mkhitaryan (Arsenal)
Landmarks for Wenger, Cech, Ozil and Arsenal – the stats
Arsene Wenger registered his 700th Arsenal win in his 1,222nd match in charge of the Gunners.
Shkodran Mustafi’s opening goal was Arsenal’s 1,000th at home in the Premier League, making the Gunners just the second team to reach the landmark after Manchester United (1,066).
Arsenal midfielder Mesut Ozil became the fastest player to reach 50 Premier League assists, doing so in just 141 games and breaking the record held by former Manchester United forward Eric Cantona (143 games).
Petr Cech made his first Premier League penalty save since February 2011 for Chelsea against Fulham – it was also the 16th he had faced in all competitions for Arsenal and the first one he had saved for the Gunners.
Cech registered his 200th Premier League clean sheet, the first goalkeeper to achieve this feat in the competition’s history.
Four of Mustafi’s five Premier League goals have been assisted by Mesut Ozil (two from corners, two from free-kicks) – all four of the Ozil-assisted goals have been at the Emirates.
Watford have now lost all five of their away Premier League matches in the month of March.
Henrikh Mkhitaryan now has the same record this season in nine appearances for Arsenal in all competitions as he did in 22 games for Manchester United (two goals, five assists).
Motty’s last live commentary
Legendary BBC commentator John Motson was on duty for BBC Radio 5 live at Emirates Stadium for his last live commentary.
Motson, 72, made his first live radio broadcast 48 years ago and during his career he covered 10 World Cups, 10 European Championships, 29 FA Cup finals and more than 200 England games.