Victor Osimhen took centre stage in Maseru with two goals and two assists as the Super Eagles showed resilience to turn around a goal deficit and grab maximum points.
Lesotho took the lead in the 11th minute after Masoabi Nkoto sent the home fans into a frenzy with his header which beat a helpless Daniel Akpeyi in goal.
Nkoto took advantage of a sloppy defence but Nigeria responded just before the half hour-mark with Alex Iwobi scoring the equaliser after benefitting from Osimhen's pass.
The three-time African champions dominated the game afterwards as Chukwueze headed the ball over an on-rushing Lichaba Thabiso in the Lesotho goal to put Nigeria in the lead in the 38th minute.
Rohr's men went into the interval ahead and started the second 45 minutes pushing for more goals.
Fresh legs were thrown into the fray with Ramon Azeez replacing Joe Aribo in the 71st minute and four minutes after the substitution, Osimhen got his moment with the third goal after a fine piece of work from Ola Aina on the left flank.
In the 85th minute, Azeez later turned provider for the fourth as Osimhen beat the goalkeeper before slotting the ball into the back of an empty net.
Just at the death of the game, Awaziem turned the ball into his own net as Lesotho reduced the deficit to 4-2.
Sunday's triumph stretches Nigeria's tally in Group L to six points after two outings while their Southern African opponents have just a single point after two games.
The Super Eagles' next group game is against Sierra Leone in August 2020.