The 29-year-old American is known for taking his matches to the wire, and it appeared to be the case in the first set as games went by way of serve.
A tie-break was needed to decide the opener, but it was an epic battle as Isner just edged it 19-17 to take a one-set lead on the grass court.
The second set was as hard-fought as the first, with both competitors holding their serves strongly, which once again forced a tie-break.
Nieminen struggled in the set decider as Isner grabbed two breaks to clinch the tie-break 7-3 to take a two-set cushion at the All England Club.
The third set appeared to be closing in on another tie-break, but Isner prevented it by securing a crucial break point to take a 6-5 lead, which allowed him to serve out for the match.