Odion Ighalo opened the scoring from the penalty spot, before Rody Melanie - against all odds and all thanks to a Francis Uzoho howler - levelled for the Pirates to end the first half in a stalemate. Goals from Henry Onyekuru and substitute Moses Simon won the game for the Super Eagles, who were unconvincing at times in the dead rubber game.
William Troost-Ekong and Kenneth Omeruo were preferred centre-back partners, with Leon Balogun - who had injury concerns before the game - left on the bench. Shehu Abdullahi regained his right-back spot after missing out on the previous games through injury.
Galatasaray winger Onyekuru made his full international debut in a competitive tie, replacing the unavailable Samuel Kalu on the right wing of a 4-3-3 formation - with Odion Ighalo leading the line.
In the fifth minute, miscommunication between the Seychelles defence and their goalie Ian Ha Kong almost gifted the hosts the lead, but they were quick to clear their lines, with Ighalo probing.
However, against the run of play, Uzoho overcame his first test, reacting quickly to palm a teasing right-wing cross. Gervais Wave-Hive tested Nigeria’s defence with a well-whipped freekick, but the Anorthosis goalie thwarted the effort.
Nigeria were edging closer to an elusive first goal with the Seychelles defence - set up in half in blocks - proving stubborn to break down.
But for a tame Ighalo effort, the Super Eagles would have opened the scoring in the 24th minute. The Shanghai Shenhua marksman could not get a proper touch on a weak Wilfried Ndidi shot, after the Leicester City midfielder skillfully worked his way into Seychelles area.
Onyekuru, largely ineffective on the right, found himself in the oppositions’ area, unmarked, but headed tamely at the goalkeeper from a fantastic Jamilu Collins cross.
The Pirates’ good work for over a half-hour was undone when Jude Nancy fell Ndidi in the box, leaving the referee no option but to point to the spot. Ighalo sent Ha Kong the wrong way to net his seventh goal of the qualifying series.
Etebo came close to doubling the Eagles’ lead almost immediately, but Ha Kong dived well to push his free-kick to safety.
Against all odds, Rody Melanie levelled for Gavin Jeanne's side after Uzoho’s howler, from an indirect free kick, gifted the visitors their second goal in qualifying.
Ighalo came close to restoring Nigeria’s lead but the woodwork came in the way of his fierce low drive and both sides went into the break on par.
Five minutes after the restart and Onyekuru redeemed his uneventful first-half showing, converting from a similar situation where he had fumbled.
The Galatasaray winger snuck behind the Pirates defence to plant Collins’ perfectly-weighted cross into the net for Nigeria to retake the lead.
In the 65th minute, Paul Onuachu was handed his debut, with Etebo making way as Rohr reshuffled things. Free-scoring Rotherham United midfielder Semi Ajayi was also drafted in for Alex Iwobi.
Ighalo made way for Simon late in the game after falling badly, but the Levante winger took the chance to make the points safe for the Super Eagles, smashing in a low effort to end the game 3-1.
The win means the Super Eagles finish their qualifying campaign - regardless of the result between Libya and South Africa in Sfax on Sunday - as Group E leader after garnering 13 points from six games, which started with a home loss against Bafana Bafana in 2017.
They continue preparation for the 2019 African Cup of Nations with a friendly encounter against Egypt at the same venue on Tuesday.