Monday night’s defeat was Portsmouth’s first at Fratton Park since September 2019 against Southampton in the League Cup (0-4), ending their 19-game unbeaten run on home soil in all competitions.
A goal in each half from from Sokratis Papasthathopoulos and Eddie Nketiah sealed the win for the Gunners.
The North London club’s January signing Pablo Mari made his debut and player for 90 minutes.
It was a positive response Arsenal after their heartbreaking loss to Olympiakos, in the Europa League on Thursday.
Arsenal were forced into an early substitute as Lucas Torreira was stretchered off and was replaced by Dani Ceballos following a tackle.
On the stroke of half-time Arsenal broke the deadlock through Papasthathopoulos who finished off Reiss Nelson’s cross.
And in the 51st minute Nketiah doubled Arsenal’s lead to send through into the next round.
Portsmouth have now failed to beat Arsenal in any competition since winning a league match 5-4 in March 1958, drawing eight and losing 14 of their 22 meetings since then.
The fifth round of the Emirates FA will continue on Tuesday, with Chelsea vs Liverpool at Stamford Bridge the standout fixture.
Other fixtures are Sheffield United away to Reading and Newcastle United traveling to the Hawthorns to face West Bromwich Albion.
Wednesday will see Sheffield Wednesday host FA Cup champions Manchester City, Leicester City will welcome Birmingham City and Tottenham Hotspur will be at home to Norwich City.
And on Thursday, Manchester United will be at Pride Park to face Derby County.