Both sides emerged from the break with attacking intent, but it was the hosts who struck first, seven minutes into the second half.
Dejan Drazic, again at the heart of the action, weaved past two defenders down the left before unleashing a fierce effort from inside the box that forced a corner.
From the short corner, Borja Herrera whipped in a pinpoint cross and Javier Siverio rose highest to nod past the goalkeeper and double FC Goa’s advantage.
Al Seeb Club responded on the hour mark after Al Sulaiman Al-Busaidi cut the ball back from the byline for Nasser Al-Rawahi to calmly slot home and halve the deficit.
The Gaurs could have opened up a two-goal cushion again in the 71st minute but Udanta Singh’s header from a Borja Herrera cross was thwarted by Al Seeb Club’s defence.
FC Goa could have put the game to bed in the 81st minute when Borja Herrera played a precise cross into the box for an unmarked Javier Siverio. The Spanish striker brought it under control and turned smartly, but dragged his effort wide of the post.
In the closing stages, Al Seeb Club threw numbers forward in search of an equaliser, but FC Goa stayed disciplined, restricting the visitors to speculative efforts from range.
A missed counter-attacking opportunity in stoppage time left the hosts under heavy pressure in the dying moments. However, resolute defending saw them survive a goalmouth scramble and repel a few dangerous set-pieces to secure a historic victory.
The Gaurs will join Mohun Bagan Super Giant in the AFC Champions League Two group stage.
Organised by the Asian Football Confederation (AFC), the AFC Champions League Two is the second-tier club football tournament on the continent after the AFC Champions League Elite.
This was FC Goa’s first piece of action on the continental stage since 2021, when the Gaurs became the first Indian football club to play in the AFC Champions League group stage.